Can adverse neonatal outcome be predicted in late preterm or term fetal growth restriction?

OBJECTIVE: To identify independent predictors of adverse neonatal outcome in cases of fetal growth restriction (FGR) at > or = 34 weeks. METHODS: From a cohort of 481 FGR cases delivered at > or = 34 weeks, demographic and obstetric variables, fetal biometry and Doppler indices of the uterine, umbilical and fetal middle cerebral arteries available within 2 weeks of delivery, were related to adverse neonatal outcome, defined as admission to the neonatal intensive care unit for indications other than low birth weight alone. RESULTS: Logistic regression analysis showed that gestational age (GA) at delivery (odds ratio (OR) = 0.59; 95% CI, 0.50-0.70), abdominal circumference (AC) centile (OR = 0.69; 95% CI, 0.59-0.81) and umbilical artery (UA) pulsatility index (PI) centile (OR = 1.02; 95% CI, 1.01-1.04) significantly correlated with adverse neonatal outcome. From this model we calculated a score of adverse neonatal outcome expressed by the formula: (UA-PI centile/3) - (10 x AC centile) + (10 x (40 - GA at delivery in weeks)). Receiver-operating characteristics curve analysis demonstrated that a score of > or = 25 optimally predicted adverse neonatal outcome (sensitivity of 75%, false-positive rate of 18%). Beyond 37.5 weeks, gestational age no longer had an independent impact on outcome. CONCLUSIONS: In late preterm or term FGR, GA at delivery is the most important predictor of adverse neonatal outcome. At > 37.5 weeks, delivery may be the best option to minimize adverse outcome in all FGR cases. At 34-37 weeks, a score based on GA at delivery, UA-PI centile and AC centile optimally predicts adverse neonatal outcome.

Are ultrasonographic myoma characteristics associated with blood loss at delivery?

OBJECTIVES: The presence of myomas in pregnancy is associated with greater blood loss at delivery. The aim of this study was to evaluate whether the sonographic characteristics of myomas can predict blood loss at delivery in women with large myomas. METHODS: Among women who underwent second-trimester ultrasound screening at our department between January 1996 and December 2004, 251 had at least one myoma with a mean diameter > or = 5 cm. Number of myomas (single vs. multiple), maximum diameter of the largest myoma, sum of the maximum diameter of each myoma, change in size of myomas between first and last scan, and location in relation to the placenta and to the presenting part of the fetus (above or below) were analyzed in relation to blood loss at delivery and severe postpartum hemorrhage (> or = 1000 mL). RESULTS: Multivariate analysis showed that the presence of multiple myomas was the only parameter independently associated with amount of blood loss at delivery (P = 0.003). The association between the presence of multiple myomas and severe postpartum hemorrhage was of borderline significance for the statistical power of this study (P = 0.08). CONCLUSIONS: In women with large myomas, the presence of multiple tumors is independently associated with heavier blood loss at delivery but not with postpartum hemorrhage of > or = 1000 mL.

Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the term given to any thromboembolic event (blocking of a blood vessel by a blood clot) occurring in the venous system. The current treatment recommended for VTE is anticoagulation (reduction of the blood's ability to clot). The aim of this review is to summarize results from randomized controlled trials (RCTs) for the effectiveness of anticoagulants (heparins, including low molecular weight heparins and vitamin K antagonists) in the treatment of VTE, compared to non-steroidal anti-inflammatory drugs (NSAIDs) or placebo. OBJECTIVES: To examine the randomized controlled evidence for the effectiveness and safety of anticoagulant treatment compared to NSAIDs or placebo in patients with VTE on the incidence of fatal and non-fatal pulmonary emboli (PE) and the recurrence or extension of deep vein thrombosis (DVT). SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialized Trials Register (last searched 26 July 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL) database (last searched Issue 3, 2005). In addition, DKC also searched reference lists and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: All randomized trials of anticoagulants versus NSAIDs or placebo in the initial treatment of VTE (DVT or PE or both). DATA COLLECTION AND ANALYSIS: DKC and JM independently assessed trial quality and extracted data. JCP (biostatistician) analyzed the design elements and feasibility of a future randomized controlled trial to determine definitively efficacy and safety of anticoagulants in VTE treatment. MAIN RESULTS: Two RCTs were included. Data were not pooled because of heterogeneity between the studies. The two RCTs were too small to determine any difference in mortality, occurrence of pulmonary emboli, progression or return of DVT between patients treated with anticoagulation and those receiving no anticoagulation. AUTHORS' CONCLUSIONS: The limited evidence from RCTs of anticoagulants versus NSAIDs or placebo is inconclusive regarding the efficacy and safety of anticoagulants in VTE treatment. The use of anticoagulants is widely accepted in clinical practice, so a further RCT comparing anticoagulants to placebo could not ethically be carried out.

Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update.

OBJECTIVE: Two recent meta-analyses have studied the association of exclusive or mainly human milk intake (HMI) on retinopathy of prematurity (ROP). One of these meta-analysis found a protective effect of only or mainly HMI on Severe ROP but not on any stage ROP. However, both these meta-analyses did not find protection from any stage ROP or Severe ROP with any amount of HMI. The objective of this study was to study the association between any amount of HMI and the development of All ROP and Severe ROP in very-low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI) by systematic review using PRISMA-P guidelines and meta-analysis. STUDY DESIGN: Exposure, controls and outcomes studied were any amount of HMI vs no HMI and All ROP/Severe ROP in VLBWI/ELBWI. All ROP was defined as all stages of ROP pooled together, and Severe ROP as ⩾stage 3 ROP and ROP requiring intervention. Results and effect sizes are expressed as odds ratio (OR), relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (95% CI). Data sources used were PubMed, MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, Scopus and CINAHL until 24 April 2015. Extracted data were pooled using a fixed effects model. Heterogeneity was assessed. Sensitivity analysis was performed. RESULTS: Five hundred nine of 1701 infants who received any amount of HMI developed All ROP vs 310 of 760 infants without HMI developed All ROP with a pooled OR 0.63* (0.51,0.78), RR 0.76* (0.67,0.86) and RD -0.09* (-0.13,-0.05). The NNT with any amount of HMI was 11* (8,20) (*P<0.0001) to prevent one case of All ROP. 204 of 2465 infants who received any amount of HMI developed Severe ROP vs 85 of 764 infants without HMI developed Severe ROP with a pooled OR 0.74* (0.56,0.98), RR 0.77* (0.60,0.98) and RD -0.03* (-0.05,-0.00). The NNT with any amount of HMI was 33* (*P=0.04) to prevent one case of Severe ROP. CONCLUSION: Any amount of HMI is strongly associated with the protection from All ROP and Severe ROP.

Increased body aluminum. An independent risk factor in patients undergoing long-term hemodialysis?

The clinical course and aluminum status of 38 patients who had been receiving dialysis for at least eight years and were still undergoing dialysis in 1985 were evaluated. Twenty-nine had evidence of increased aluminum burden, although only three had evidence of overt aluminum toxicity, and nine did not have evidence of increased aluminum burden. The patients in both the high- and low-aluminum group were similar with regard to age, the cause of their renal failure, presence of hypertension or coronary artery disease, previous parathyroidectomy, and a number of biochemical parameters, along with the amount of prescribed aluminum. All patients were followed up for the next two years or until they died. The amount of ingested aluminum was reduced, and in selected patients, treatment with intermittent infusions of deferoxamine mesylate was instituted. There were no deaths in the low-aluminum group, but ten of 29 died in the high-aluminum group: seven of vascular disease and three of infection. In addition, morbidity as defined by hospitalization for coronary or cerebral vascular disease or infection occurred in only two of the nine patients in the low-aluminum group and in 19 of the 29 patients in the high-aluminum group. These observations imply that the occurrence of increased body aluminum, as suggested by aluminum blood levels or by results of bone biopsies in some patients, has an adverse effect on morbidity and mortality and should be considered as a possible independent risk factor in patients who are receiving long-term hemodialysis.

Predictive value of preoperative tests in discriminating bilateral adrenal hyperplasia from an aldosterone-producing adrenal adenoma.

In primary hyperaldosteronism, discriminating bilateral adrenal hyperplasia (BAH) from an aldosterone-producing adenoma (APA) is important because adrenalectomy, which is usually curative in APA, is seldom effective in BAH. We analyzed the results from our most recent 7-yr series to evaluate the predictive value of preoperative noninvasive tests compared with adrenal vein sampling (AVS). Forty-eight patients with hypertensive hyperaldosteronism underwent bedside testing, computed tomography (CT) imaging, and AVS. Those in whom the results of AVS indicated APA underwent adrenalectomy. Twelve (30%) and 14 (34%) of 41 patients with APA had paradoxical falls with ambulation in plasma aldosterone concentration (PAC) and 18-hydroxycorticosterone (18-OH-B), respectively. Twenty-nine (70%) and 26 (65%) APA patients had a rise in PAC and 18-OH-B, respectively, as did all 8 BAH patients. Significant identifiers of BAH were supine PAC values less than 15 ng/dL (P: = 0.04), an increase greater than 60% (P: = 0.02) in PAC with ambulation, and supine 18-OH-B values less than 60 ng/dL (P: = 0.04). CT imaging alone was not predictive for BAH or APA. In our population, patients with a positive bedside test result (e.g. a fall in PAC and/or 18-OH-B) and a unilateral adrenal nodule on CT (10 of 41 patients) could have proceeded directly to adrenalectomy for APA. However, a positive bedside test result with a negative CT or a negative bedside test result regardless of CT findings required AVS to confirm the diagnosis and site of disease.

A longitudinal study of atlanto-dens relationships in asymptomatic individuals with Down syndrome.

This study was designed to investigate the natural history of atlantoaxial instability in individuals with Down syndrome and to determine whether significant changes in C1-C2 relationship are taking place over time. Although more than 400 patients with Down syndrome who are presently followed at the Child Development Center had cervical spine radiographic examinations in the past, only 141 patients who had serial radiological examinations and whose radiographs were available for reevaluation participated in this study. The results of our investigations revealed that there were only minor changes (1 to 1.5 mm) of atlanto-dens interval measurements over time in 130 (92%) patients with Down syndrome. Eleven patients (8%) had changes of atlanto-dens interval measurements between 2 and 4 mm over time; however, none of these patients had any clinical symptoms. The analyses of data obtained from several subgroups (males and females, various age groups, and patients with and without atlantoaxial instability) did not show any significant changes of atlanto-dens interval measurements of successively obtained radiographs. Our recommendations for and rationale of routine screening for atlantoaxial instability and follow-up examinations are discussed in detail.

Radiation dose from radiopharmaceuticals contaminated with molybdenum-99.

Sixteen patients undergoing routine nuclear imaging procedures were injected with 99mTc-labeled radiopharmaceuticals containing 99Mo which exceeded the recommended limit of 1 microCi of 99mMo per mCi of 99mTc. The kinetics of the resulting 99Mo distribution in 14 of these patients were studied over a period of several weeks. The mean biologic half-life [T 1/2b] ranged from about 19.3 days to 11.2 days depending on the model used. Similarly, the mean radiation dose to the liver ranged from approximately 0.02 rad/microCi of 99Mo to 0.05 microCi of 99Mo.

Antenatal corticosteroids and placental histology in preterm birth.

To assess the effects of antenatal corticosteroid use on placental histopathology, we have reviewed a database of 463 consecutive non-anomalous singleton liveborns delivered at less than 32 weeks between April 1988 and December 1994, of which 280 received one or more doses of corticosteroids for promotion of fetal lung maturation. Patients were grouped by the number of corticosteroid doses received (analyzed as none, 1, 2 and 3 or more doses). Clinical and demographic factors were recorded prospectively. Placental histopathology was reviewed blinded to clinical factors except gestational age, and 42 distinct placental lesions were examined and scored for severity. Data were analyzed by contingency tables, one-way analysis of variance, and linear regression analysis. Among clinical variables, univariate analysis showed that the number of corticosteroid doses was significantly related to presence of labour prior to delivery, pre-eclampsia, premature rupture of membranes and clinical suspicion or diagnosis of chorioamnionitis. Using linear regression analysis with these clinical variables as confounders, increased number of doses of antenatal corticosteroids was related to increased severity of villous fibrosis and stromal mineralization, and fewer villous infarcts.

Risk factors for neonatal intraventricular haemorrhage in spontaneous prematurity at 32 weeks gestation or less.

In this study we aimed to establish which clinical and histopathological factors are associated with early-onset neonatal intraventricular haemorrhage (IVH) in non-iatrogenic preterm delivery before 32 weeks of gestation. We retrospectively reviewed all singleton pregnancies delivered before 32 weeks of gestation after spontaneous onset of preterm labour or preterm membrane rupture during the period January 1993 to June 1997. Clinical and histopathological data in cases with IVH diagnosed at neonatal cranial ultrasound within 72 h of birth (n = 17) were compared with those of neonates not experiencing this complication (non-IVH) (n = 54). Histological lesions analysed were those of acute inflammation and those on a uteroplacental vascular basis. Statistical methods included the Wilcoxon rank sum test, Fisher's exact test, and logistic regression analysis. A P<0.05 was considered significant.IVH and non-IVH groups were not significantly different in birthweight, gestational age at delivery, cord pH at birth, rates of 5-min Apgar score below 7, caesarean delivery, diagnosis of clinical chorioamnionitis or antenatal administration of steroids. Respiratory distress syndrome was more frequently diagnosed in the IVH than non-IVH group (64 per cent versus 33 per cent, P=0.02). Placental acute inflammatory or uteroplacental vascular lesions were present in 100 per cent of IVH neonates versus 22 per cent of non-IVH cases (P<0.001). Logistic regression analysis demonstrated that only respiratory distress syndrome (P = 0.04) and histological evidence of acute placental inflammation (P = 0.02) were significantly and independently associated with IVH. Histopathological evidence of acute inflammatory placental lesions is the best predictor of occurrence of neonatal IVH.

Clinical correlations of patterns of placental pathology in preterm pre-eclampsia.

The objective of this study was to determine if placental histopathology patterns are associated with clinical features of preterm pre-eclampsia. A 1989-1993 database of consecutive non-anomalous singleton livebirths delivered at 22-32 weeks gestation excluding cases of maternal diabetes mellitus and chronic hypertension included 74 cases of pre-eclampsia. Placentae were scored for uteroplacental vascular lesions and lesions of chronic inflammation and coagulation. Thirteen lesion patterns identified by factor analysis were studied in relation to the clinical features. Severe maternal proteinuria was related to placental chronic inflammation, while lower maternal antepartum platelet counts were related to placental abruption and infarct. Lower birthweight percentile and lighter placentae were related directly to uteroplacental vascular lesions. Diagnosis of HELLP and coagulopathy were less common when chronic inflammation scores were high. Serologic studies related to autoimmunity and maternal blood pressures were unrelated to placental histopathology factors. It is concluded that features of maternal and fetal compromise in preterm pre-eclampsia are related to placental histopathology patterns.

Risk for trisomy 21 in offspring of individuals who have relatives with trisomy 21.

This study was performed to determine if sibs and other relatives of individuals with trisomy 21 are themselves at increased risk for having offspring with trisomy 21. The results suggest that the reproductive risk to these relatives is not increased beyond the risk to the general population.

Gastric adenocarcinoma: prognostic significance of several pathologic parameters and histologic classifications.

Considerable controversy exists about the value of histologic classifications of gastric adenocarcinoma in the prediction of patient survival. Histologic sections of 75 consecutive gastrectomies were used to compare Lauren and Ming classifications with emphasis on clinical stage, size, location of tumor, desmoplasia, inflammatory reaction, and 5-year survival. Both classifications generally correlated and, when combined, proved helpful in defining certain cases. At surgery, about one third of the total cases of intestinal (INT, Lauren) and expanding (ET, Ming) were in early stages, whereas almost all the diffuse (DT, Lauren) and infiltrative (INF, Ming) types were in late stages. When the Lauren classification was applied to preoperative endoscopic biopsies, a 72% diagnostic correlation with the surgical specimens was found. Followup revealed no survivors of the DT and INF and 12 and 11 survivors of INT and ET, respectively, regardless of stage. Inflammatory response was associated with good prognosis. Desmoplasia and size had no prognostic significance. Tumors of the cardia had worse prognoses than those in the body or antrum. Both Lauren and Ming classifications, and especially the degree of inflammation, were significant in predicting survival. Lauren INT and Ming ET should be declared only when they are the sole or predominant features.

Quantitative differences in arterial morphometry define the placental bed in preeclampsia.

The purpose of this study was to quantitatively analyze normal and preeclamptic uteroplacental vasculature. Myometrial arteries from eight placental bed biopsies from uncomplicated term deliveries and 12 from proteinuric preeclampsia were characterized as uteroplacental, spiral, or basal arteries. Basal lumens within 0.2 mm radius and spiral/uteroplacental lumens within 0.4 mm radius were considered as the same artery. The biopsy area, lumen density, and arterial density (after correction for multiple lumens), lumen area, lumen perimeter, mean wall thickness, inflated diameter, and a slant factor, measuring the obliqueness of arterial transection, and ratios of lumen characteristics to mean wall thickness were analyzed. In preeclamptic cases, there were more basal lumens/mm2 and basal arteries/mm2 (P=.003, P=.03), and more spiral lumens/mm2 and spiral arteries/mm2 (P = .01, P = .03). Basal lumen area (P = .0003) and wall thickness (P = .007), and basal and spiral artery lumen perimeters and inflated diameters (for each, P = .0001, P = .048, respectively) and inflated diameter/wall ratios (P = .04, P = .05) were reduced compared with normal cases. Preeclamptic spiral and basal arteries are more tortuous or densely distributed than normal placental bed arteries, with smaller-caliber lumens and thicker walls. Failure of proper placentation may result in abnormal spatial anatomy in the placental bed. Alternatively, an anatomic variant of spiral and basal arteries may be more susceptible to hemodynamic stresses and endothelial damage and may predispose to preeclampsia.

Placental vascular lesions and likelihood of diagnosis of preeclampsia.

OBJECTIVE: To test the hypothesis that a range of severity of placental vascular lesions underlies preeclampsia and that the likelihood of its clinical diagnosis increases with the extent and severity of uteroplacental vascular lesions. METHODS: Four hundred sixty-five consecutive placentas of singleton, nonanomalous, live-born infants born before 32 weeks' gestation were examined prospectively, and uteroplacental vascular and related villous lesions were assigned a semiquantitative lesion score based on severity and extent of lesions. The summed scores of individual lesions yielded a total uteroplacental vascular lesion score, ranging from 0 to 21, that was correlated with the odds of a clinical diagnosis of preeclampsia, as well as with potential confounders, including maternal age, race, gestational age at delivery, and birth weight centile. Statistical analysis was performed using contingency tables, one-way analysis of variance, multiple logistic regression, and receiver operating characteristic curve. P < .05 was considered significant. RESULTS: A clinical diagnosis of preeclampsia was present in 78 of 465 (17%) cases. Logistic regression demonstrated that the total uteroplacental vascular lesion score related significantly to the diagnosis of preeclampsia (odds ratio 1.43, 95% confidence interval 1.31, 1.57) and this association was independent of gestational age at delivery and birth weight centile. Preeclampsia was diagnosed in 12 of 284 (4%) cases with no or minimal histologic evidence of placental vascular injury (total score less than 4). Conversely, the diagnosis was not made in 4% of cases despite the presence of extensive placental vascular injury (total score at least 14). CONCLUSION: The likelihood of clinical diagnosis of preeclampsia before 32 weeks increases with progressive impairment of the uteroplacental circulation. Histopathologic examination of the placenta can be used to confirm the diagnosis of preeclampsia.

Placental and decidual histology in spontaneous abortion: detailed description and correlations with chromosome number.

OBJECTIVES: To determine the histopathology of failed pregnancy in clinically symptomatic women with no more than one prior pregnancy loss in order to provide baseline data, and to determine whether the histology of the conceptus in spontaneous abortions could predict a normal or abnormal chromosome number. METHODS: A review of all spontaneous abortions from which karyotypes were obtained between 1984-1991 yielded 224 cases in which maternal history indicated no more than one prior spontaneous abortion, a reliable date of last menstrual period (LMP), and available villous (221) and/or decidual/implantation site (175) pathology. Molar pregnancies were excluded. RESULTS: Multivariate logistic regression analysis showed a significant relationship between chromosome number and gestational age at loss as calculated from the LMP. Considering this confounder, a villous circulation indicating fetal life to 11 or more weeks, chronic intervillositis and villous infarcts (each P < .01), and decidual vasculitis (P < .05) were more frequent in chromosomally normal conceptions. Substituting possible variables into the logistic regression equation yielded predictions ranging from 88% likelihood of chromosomal abnormality to 97% likelihood of normal chromosome number. CONCLUSIONS: Histology can assist in assessing whether a spontaneous abortion is chromosomally normal or abnormal. There are many pathologic findings seen in spontaneous abortions regardless of karyotype; however, certain findings are more common in chromosomally normal abortions. These data provide a baseline for study of the histopathology of habitual abortion.

Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses.

OBJECTIVE: To identify placental histopathology associated with absent and reversed end-diastolic flow demonstrated by umbilical artery (UA) Doppler velocimetry in fetal growth restriction (FGR). METHODS: Between January 1989 and June 1995, 64 consecutive, nonanomalous singletons at less than the tenth percentile for birth weight were admitted to the neonatal intensive care unit, with UA Doppler velocimetry obtained within 3 days of delivery; 54 of the 64 (84%) had placental histopathology. Umbilical artery Doppler wave forms were classified as having end-diastolic flow (n = 26), and either absent (n = 20) or reversed end-diastolic flow (n = 8). Blinded review of placental histology scored lesions in categories of intraplacental vaso-occlusion, uteroplacental vascular pathology, chronic inflammation, and coagulation. RESULTS: Using cases of FGR with end-diastolic flow present as the control population, we found that absent end-diastolic flow cases had significantly more fetal stem vessels with medial hyperplasia and luminal obliteration, and cases of reversed end-diastolic flow had significantly more poorly vascularized terminal villi, villous stromal hemorrhage, "hemorrhagic endovasculitis," and abnormally thin-walled fetal stem vessels (each P < .005). CONCLUSION: In FGR, UA Doppler velocity wave forms do not demonstrate a continuum of placental lesions in which reversed end-diastolic flow reflects more severe placental histopathology than absent end-diastolic flow and end-diastolic flow present. As expected, absent end-diastolic flow cases had more occlusive lesions of the intraplacental vasculature. In reversed end-diastolic flow, lesions suggesting vascular remodeling and/or damage by pathologic conditions of intraplacental flow predominated.

Elevated second-trimester maternal serum hCG: a marker of inadequate angiogenesis.

OBJECTIVE: To measure angiogenin, a potent inducer of neovascularization and interleukin-6, as an indicator of acute inflammation, in second-trimester amniotic fluid of patients with elevated maternal serum hCG. METHODS: In this case-control study, 20 patients with elevated maternal serum hCG (at least 2.0 multiples of median) at triple screen were matched 2:1 with controls on the basis of year of amniocentesis, parity, and race. Inclusion criteria were 1) singleton gestation, 2) no evidence of anomalies, and 3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin and interleukin-6. The immunoassay sensitivity for angiogenin was 0.026 ng/mL, interassay coefficient of variation 4.6%, and intra-assay coefficient of variation 2.9%. For interleukin-6, the immunoassay sensitivity was 2.37 pg/mL, interassay coefficient of variation 2.7%, and intra-assay coefficient of variation 1.9%. Angiogenin and interleukin-6 values were normalized by using natural log transformation for statistical analysis. Statistical analysis included analysis of variance and stepwise regression, with P < .05 significant. RESULTS: After correcting (by multivariate regression) for gestational age at sampling and nulliparity, amniotic fluid angiogenin levels were significantly lower in the study subjects than in controls (26%+/-11% lower, P=.004), whereas the interleukin-6 levels did not change significantly (34%+/-40% lower, P=.3). CONCLUSION: Amniotic fluid angiogenin levels are significantly lower in patients with elevated maternal serum hCG at triple screen, suggesting inadequate angiogenesis, but interleukin-6 values do not differ significantly.

Circulating levels of IGFs and IGF binding proteins in human cord serum: relationships to intrauterine growth.

Cord sera were obtained from 44 term, human infants exhibiting various patterns of intrauterine growth and were assayed for IGF-1, IGF-2, and IGFBP-1, 2, and 3 by specific RIAs. Serum levels were correlated with birth weight (BW), ponderal index (PI), and placental weight (PW). Total IGF-1 levels correlated significantly with BW (r = 0.392), PW (r = 0.351), and PI (r = 0.481). By contrast, the correlation of IGF-2 with birth weight was not statistically significant (r = 0.264, P = 0.091). The association of IGF-2 with PI, however, was significant (r = 3.348, P = 0.024). IGFBP-3 exhibited significant correlations with BW, PI, and PW, similar to those seen with IGF-1. IGFBP-1 and IGFBP-2, however, were not significantly related to growth parameters. IGF-1 levels correlated strongly with IGFBP-3 levels (r = 0.646, P = 0.001). By contrast, IGF-1 correlated with the reciprocal of both IGFBP-1 and IGFBP-2. Based upon in vitro affinity constants, theoretical concentrations for each [IGF/IGFBP] complex, free IGFs, and free IGFBPs were calculated for each infant. Multiple regression analysis was performed including all 11 calculated variables and correlated with each growth parameter. This analysis revealed that an integrated expression of IGF activity exhibited stronger correlations with growth than each individual peptide species (BW, r = 0.681; PI, r = 0.660; PW, r = 0.658). These data further support roles for IGF related peptides (IGFRPs) in human fetal and placental growth and suggest regulatory/counterregulatory roles for the IGFBPs. It also supports the hypothesis that individual IGFRPs interact in a complex manner to define 'net IGF activity' in relation to fetal growth and/or metabolic status.

Differing susceptibility of echocardiographic contrast agents to adverse effects of biologic factors: multicenter, videodensitometric comparison of octafluoropropane-filled microspheres with air-filled microspheres for left ventricular opacification.

BACKGROUND: Echocardiographic contrast enhancement of the left ventricle has diagnostic value in the assessment of regional and global left ventricular (LV) function. The efficacy of both octafluoropropane-filled human albumin microbubbles (OCTA) and of air-filled human albumin microbubbles (AIR) for LV endocardial delineation and qualitative LV opacification has previously been reported. However, pulmonary disease, obesity, impaired LV function, and decreased echogenicity may diminish the efficacy of contrast agents for LV opacification. The purpose of this study was to compare the susceptibility of 2 contrast agents currently approved by the Food and Drug Administration to these biologic factors. METHODS: To compare quantitative LV opacification with OCTA (0.2, 0. 5, 3.0, 5.0 mL) versus AIR (0.08 mL/kg, 0.22 mL/kg), we performed videodensitometry in 199 patients (average age 59.2 +/- 13.3 years, 79% men) studied in 2 identical, prospective, multicenter, blinded trials, of whom 74 had impaired LV function, pulmonary disease, or both, 70 were obese (body mass index >30 kg/m(2)), and 45 were nonechogenic (>/=4 of 6 endocardial segments were not seen in the apical 4-chamber view). Changes in videodensity from noncontrast to contrast agent with the same gain settings were determined at end diastole and end systole (gray scale 0 to 255 U) for 2 regions of interest: left ventricle apex-to-mid-cavity and mid-cavity-to-base. The relative influence of clinically evident pulmonary disease, impaired LV function on echocardiography, and echogenicity on LV opacification produced by both contrast agents was determined by multivariate analysis. RESULTS: Significant videodensity increases ranging from 67% to 143% were observed with both agents. At the recommended initial doses (0.5 mL for OCTA, 0.22 mL/kg for AIR), OCTA produced greater opacification than AIR in both regions of interest and at both phases of the cardiac cycle. Poor LV function was associated with decreased LV opacification for AIR but not for OCTA. Diminished echogenicity was more strongly associated with impaired opacification for AIR than for OCTA. Obesity and clinically evident pulmonary disease were associated with diminished chamber opacification with both OCTA and AIR. CONCLUSIONS: In addition to the superiority of octafluoropropane-filled microspheres to air-filled microspheres for LV opacification, the efficacy of OCTA is relatively unaffected by impaired LV function and is less susceptible to the effects of poor echogenicity than AIR.