Intrapartum fever, epidural analgesia and histologic chorioamnionitis.

OBJECTIVE: Our objective was to determine whether epidural analgesia and histologic chorioamnionitis were independent predictors of intrapartum fever. STUDY DESIGN: This secondary analysis, retrospective cohort study included term parturients with placental examination during 2005. Logistic regression used fever (⩾38 °C) as the dependent variable. Significance was defined as P⩽0.05. RESULT: There were 488 (76%) of 641 term parturients with placental examination and epidural. Independent predictors of intrapartum fever were epidural odds ratio (OR)=3.4, confidence interval (CI): 1.70, 6.81, histologic chorioamnionitis OR=3.18, 95% CI: 2.04, 4.95, birthweight OR=2.07, 95%CI: 1.38, 3.12, vaginal exams OR=1.15, 95% CI:1.06, 1.24, duration ruptured membranes OR=1.03, 95% CI: 1.01,1.05, parity⩾1 OR=0.44: 0.29, 0.66 and thick meconium OR=0.35: 95%CI: 0.24, 0.85. CONCLUSION: Epidural analgesia and histologic chorioamnionitis were independent predictors of intrapartum fever. Modification of labor management may reduce the incidence of intrapartum fever.

Accuracy of signs of clinical chorioamnionitis in the term parturient.

OBJECTIVE: Uniform histopathologic guidelines were applied to diagnose chorioamnionitis and estimate the accuracy of clinical signs in term parturients. STUDY DESIGN: A retrospective cohort study utilized slides from term parturient placentas with Amniotic Fluid Infection Nosology Committee guidelines as the gold standard. Sensitivity, specificity and accuracy for fever, maternal tachycardia and fetal tachycardia were calculated. RESULT: Of 641 placentas, 367 (57.3%) had histologic chorioamnionitis and 274 (42.7%) were negative. Fever had a sensitivity of 42%, specificity of 86.5% and accuracy of 61%. Fever, maternal tachycardia and fetal tachycardia had a sensitivity of 18.3%, specificity of 98.2% and accuracy of 52.4%. CONCLUSION: Histologic chorioamnionitis, frequently asymptomatic, is a common finding in placentas examined from term parturients. Clinical signs are not accurate in the diagnosis. Adoption of uniform pathologic guidelines will facilitate research into the clinical significance of these lesions in the future.

Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia.

An abnormal pulmonary vasculature may be an important component of bronchopulmonary dysplasia (BPD). We examined human infant lung for the endothelial cell marker PECAM-1 and for angiogenic factors and their receptors. Lung specimens were collected prospectively at approximately 6 h after death. The right middle lobe was inflation fixed and part of the right lower lobe was flash frozen. We compared lungs from infants dying with BPD (n = 5) with lungs from infants dying from nonpulmonary causes (n = 5). The BPD group was significantly more premature and had more days of ventilator and supplemental oxygen support, but died at a postconceptional age similar to control infants. PECAM-1 protein and mRNA were decreased in the BPD group. PECAM-1 immunohistochemistry showed the BPD group had decreased staining intensity and abnormal distribution of alveolar capillaries. The dysmorphic capillaries were frequently in the interior of thickened alveolar septa. The BPD group had decreased vascular endothelial growth factor (VEGF) mRNA and decreased VEGF immunostaining, compared with infants without BPD. Messages for the angiogenic receptors Flt-1 and TIE-2 were decreased in the BPD group. We conclude that infants dying with BPD have abnormal alveolar microvessels and that disordered expression of angiogenic growth factors and their receptors may contribute to these abnormalities.

Simulation of ultrasonic pulse propagation, distortion, and attenuation in the human chest wall.

A finite-difference time-domain model for ultrasonic pulse propagation through soft tissue has been extended to incorporate absorption effects as well as longitudinal-wave propagation in cartilage and bone. This extended model has been used to simulate ultrasonic propagation through anatomically detailed representations of chest wall structure. The inhomogeneous chest wall tissue is represented by two-dimensional maps determined by staining chest wall cross sections to distinguish between tissue types, digitally scanning the stained cross sections, and mapping each pixel of the scanned images to fat, muscle, connective tissue, cartilage, or bone. Each pixel of the tissue map is then assigned a sound speed, density, and absorption value determined from published measurements and assumed to be representative of the local tissue type. Computational results for energy level fluctuations and arrival time fluctuations show qualitative agreement with measurements performed on the same specimens, but show significantly less waveform distortion than measurements. Visualization of simulated tissue-ultrasound interactions in the chest wall shows possible mechanisms for image aberration in echocardiography, including effects associated with reflection and diffraction caused by rib structures. A comparison of distortion effects for varying pulse center frequencies shows that, for soft tissue paths through the chest wall, energy level and waveform distortion increase markedly with rising ultrasonic frequency and that arrival-time fluctuations increase to a lesser degree.

The effect of abdominal wall morphology on ultrasonic pulse distortion. Part I. Measurements.

The relative importance of the fat and muscle layers of the human abdominal wall in producing ultrasonic wavefront distortion was assessed by means of direct measurements. Specimens employed included six whole abdominal wall specimens and twelve partial specimens obtained by dividing each whole specimen into a fat and a muscle layer. In the measurement technique employed, a hemispheric transducer transmitted a 3.75-MHz ultrasonic pulse through a tissue section. The received wavefront was measured by a linear array translated in the elevation direction to synthesize a two-dimensional aperture. Insertion loss was also measured at various locations on each specimen. Differences in arrival time and energy level between the measured waveforms and computed references that account for geometric delay and spreading were calculated. After correction for the effects of geometry, the received waveforms were synthetically focused. The characteristics of the distortion produced by each specimen and the quality of the resulting focus were analyzed and compared. The measurements show that muscle produces greater arrival time distortion than fat while fat produces greater energy level distortion than muscle, but that the distortion produced by the entire abdominal wall is not equivalent to a simple combination of distortion effects produced by the layers. The results also indicate that both fat and muscle layers contribute significantly to the distortion of ultrasonic beams by the abdominal wall. However, the spatial characteristics of the distortion produced by fat and muscle layers differ substantially. Distortion produced by muscle layers, as well as focal images aberrated by muscle layers, show considerable anisotropy associated with muscle fiber orientation. Distortion produced by fat layers shows smaller-scale, granular structure associated with scattering from the septa surrounding individual fat lobules. Thick layers of fat may be expected to cause poor image quality due to both scattering and bulk absorption effects, while thick muscle layers may be expected to cause focus aberration due to large arrival time fluctuations. Correction of aberrated focuses using time-shift compensation shows more complete correction for muscle sections than for fat sections, so that correction methods based on phase screen models may be more appropriate for muscle layers than for fat layers.

Fibronectin expression in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic fibrotic lung disease of neonates. Fibronectin (FN), a component of the extracellular matrix, is increased in the tracheobronchial effluent of neonates destined to develop BPD. Pulmonary FN is derived from plasma and local cellular synthesis. In order to identify which pulmonary cells synthesize FN and to test the hypothesis that FN is more abundant in lungs with BPD, we examined the distribution of pulmonary FN by in situ hybridization (for mRNA) and immunohistochemistry (for protein) in neonatal autopsy lung specimens, comparing lungs with BPD to those without. We used a staging system in which BPD is characterized by disruption of alveolar architecture, severe vascular changes, airway epithelial necrosis, smooth muscle hypertrophy, and peribronchial fibrosis. FN mRNA and protein were found in vascular endothelium, macrophages, fibroblasts, vascular and airway smooth muscle, and chondrocytes as well as in the pulmonary parenchyma in neonates with and without BPD. Hyaline membranes, when present, immunostained intensely for FN protein. FN mRNA was not seen in airway epithelial cells of either group. FN mRNA and protein were first increased in early acute BPD with their levels appearing greatest during the chronic reparative stage of BPD. In long-standing "healed" BPD, lower levels of FN mRNA and protein were seen. These findings are consistent with the association of increased FN with adult fibrotic lung disease and the previously reported increase in FN tracheal effluent levels in infants with BPD. Our results suggest an important role for pulmonary cell-derived FN in the early inflammatory and later proliferative stages of BPD.

Absidia corymbifera infections in neonates.

We report the first two documented cases of neonatal zygomycosis caused by Absidia corymbifera. A premature infant developed disseminated disease from a cutaneous site with pulmonary, gastrointestinal, and cerebral involvement. The infant died despite amphotericin B therapy and surgical debridement. The second case occurred in a full-term infant with congenital heart disease and fungal pneumonitis. Zygomycosis was not suspected because of underlying cardiac disease and a complicated postoperative course, and this infant also died. Absidia joins a growing list of opportunistic fungal pathogens of the compromised neonate.

Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease.

A major clinical challenge in Gaucher disease is the early and presymptomatic discrimination of type 2 (acute neuronopathic) from milder type 1 and type 3 Gaucher patients to enable appropriate management and counseling. Although most patients with Gaucher disease do not have skin abnormalities, a subset of patients with severe type 2 Gaucher disease display ichthyosiform skin. Analogous findings occur in the skin of type 2 (null allele) Gaucher mice. Ultrastructural and functional studies of epidermis from these mice reveal that glucocerebrosidase is required to generate functionally competent membranes for normal epidermal barrier function. We have extended our studies by examining the epidermal lipid content and ultrastructure in all three types of Gaucher patients. Only the type 2 Gaucher patients, some of whom had clinical ichthyosis, demonstrated an increased ratio of epidermal glucosylceramide to ceramide as well as extensive ultrastructural abnormalities, including the persistence of incompletely processed lamellar body-derived contents throughout the stratum corneum interstices. These epidermal alterations may provide a means for early differentiation of type 2 Gaucher disease.

Maternal prepregnant weight and weight gain: relationship to placental microstructure and morphometric oxygen diffusion capacity.

This study examines the effects of maternal prepregnant weight and gestational weight gain on the size, microstructure, and function of the human placenta. Standard gross, histologic, and histomorphometric techniques were used to examine placentas obtained from the deliveries of 77 poor, black 12- to 30-year-old subjects in relation to maternal prepregnant weight and the rate of maternal weight gain during gestation. The weight, volume, and fetal capillary surface area of the placenta increased significantly in relation to both maternal prepregnant weight and the rate of maternal weight gain during gestation. Prepregnant weight was a more important determinant of placental size and fetal capillary surface area than was the rate of maternal weight gain. The rate of maternal weight gain was a more important determinant of the density of fetal capillary tissues within the placenta and of placental resistance to oxygen diffusion than was prepregnant weight. Both maternal prepregnant weight and the rate of maternal weight gain during gestation relate positively to the size of the placenta, but they have different, potentially complementary effects on placental microstructure and function.

Lack of mandibular movement manifested by absent fetal swallowing: a possible factor in the pathogenesis of micrognathia.

This study was performed to assess the association of lack of mandibular movement as manifested by absent fetal swallowing and micrognathia in a nonrestrictive intrauterine environment. Over a 5-year period, 14 fetuses with sonographic findings of polyhydramnios (amniotic fluid index [AFI] more than 20 cm), absent mandibular movement, and a nonvisualized fetal stomach, all consistent with absent fetal swallowing, were followed. A group of 14 fetuses, each with polyhydramnios (AFI more than 20 cm), yet with sonographic detection of fetal swallowing, served as controls. All gravidas in both groups were normoglycemic throughout gestation. Subsequent mandibular development was assessed at delivery or autopsy. Analysis of the data revealed that in the study group, 12 of these infants were liveborn, and two were stillborn. Eleven of the liveborn infants had an early neonatal death. All 14 infants of the study group demonstrated micrognathia. None of the control infants (all of whom survived) had micrognathia. In conclusion, this study supports the concept that normal mandibular growth may depend on the presence of mandibular movement during intrauterine development.

Marked twin-twin transfusion in the absence of nonimmune hydrops.

The precise pathophysiology of development of nonimmune hydrops in either the recipient or donor twin associated with twin-twin transfusion syndrome is not entirely clear. At times the recipient twin may develop nonimmune hydrops, but at other times the donor twin, and infrequently both, may develop this ominous complication. We present an unusual cases of this syndrome in which discordant twins, despite neonatal hematocrit levels of 86 and 21% were both nonhydropic and discuss the possible underlying pathophysiology of this occurrence.

Placental metastases in a patient with recurrent breast carcinoma.

We present an unusual case of extensive placental micrometastases of recurrent breast carcinoma. The discrepancy between the gross and histopathologic findings in this case suggests that in the absence of gross metastases, meticulous microscopic examination may reveal a higher incidence of metastases than has been reported previously.

Association of in utero behavioral patterns of twins with each other as indicated by fetal heart rate reactivity and nonreactivity.

Prospective analysis of 75 pairs of nonstress tests (NSTs) obtained simultaneously from both members of 35 twin gestations was performed to quantitatively assess the incidence of simultaneous periods of fetal heart rate (FHR) reactivity and nonreactivity of twins. Comparative analysis of the paired NSTs was used to compute rates of simultaneous fetal heart rate reactivity and nonreactivity. Statistical analysis involved comparison of weighted averages of these rates, using sequence lengths as weights. Weighted standard deviations were used to describe variability between sets of NSTs. Trend analysis was performed using weighted linear regression to calculate slopes for pairs of twins with three or more repeat NSTs. Groups of twins were compared by performing a variance stabilizing transformation on the appropriate rates, and using a two sample t test to compare the means of transformed data. Analysis of this data revealed that twins exhibited similar in utero fetal heart reactivity and nonreactivity as indicated by simultaneous electronic fetal monitoring during 79.90% +/- 1.62 (SD) of the time monitored. The incidence of periods of simultaneously reactive FHR and simultaneously nonreactive FHR were 11.79% +/- 1.02 and 68.10% +/- 2.17, respectively, irrespective of gestational age. These data confirm the hypothesis that periods of FHR reactivity and nonreactivity of twins are strongly associated with each other.

Prenatal sonographic diagnosis of non-rhizomelic chondrodysplasia punctata.

BACKGROUND: Chondrodysplasia punctata is a rare heterogeneous group of bone dysplasias occurring with an incidence of one in 100,000 live births. Prenatal sonographic diagnosis of non-rhizomelic chondrodysplasia punctata (Conradi-Hünermann syndrome) has previously been reported only following detection of overall limb shortening. CASE: Multiple sonographic skeletal findings of premature epiphyseal calcifications, other unusual calcifications, kyphoscoliosis, and asymmetrical limb shortening, typical of non-rhizomelic chondrodysplasia punctata, led to second-trimester prenatal sonographic diagnosis of this condition. CONCLUSION: Second-trimester prenatal sonographic diagnosis of premature epiphyseal calcifications associated with non-rhizomelic chondrodysplasia punctata is possible.

Measurements of ultrasonic pulse arrival time and energy level variations produced by propagation through abdominal wall.

Ultrasonic pulse arrival time and energy level variations introduced by propagation through human abdominal wall specimens have been measured. A hemispheric transducer transmitted an ultrasonic pulse that was detected by a linear array transducer after propagation through an abdominal wall section. The array was translated in the elevation direction to collect data over a two-dimensional aperture. Differences in arrival time and energy level between the measured waveforms and calculated references that account for geometric delay and spreading were found. Plots of waveforms compensated for geometric path, maps of time delay differences and energy level fluctuations, and statistics derived from these for water paths and tissue paths characterize the measurement system and describe the time delay differences and energy level fluctuations caused by 14 different human abdominal wall specimens. Repeated measurements using the same specimens show that individual tissue path measurements are reproducible, the results depend on specimen position, and frozen storage of a specimen for three months does not appear to alter the time delay differences and energy level fluctuations produced by the specimen. Comparison of measurements at room and body temperature indicates that appreciably higher time delay differences occur at body temperature while energy level fluctuations and time delay difference patterns are less affected. For the 14 different abdominal wall specimens, the rms time delay differences and energy level fluctuations have average values of 43.0 ns and 3.30 dB, respectively, and the associated correlation lengths of the time delay differences and energy level fluctuations are 7.90 and 2.28 mm, respectively. The spatial patterns of time delay difference and energy level fluctuation in the reception plane appear largely uncorrelated, although some background variations in energy level fluctuation are similar to features in time delay difference maps. The results provide important new information about the variety and range of ultrasonic wave front arrival and energy variations caused by transmission through abdominal wall.

Prenatal sonographic assessment of early, rapidly growing fetal cervical teratoma.

Although malignant transformation of fetal cervical teratoma is extremely rare, perinatal morbidity is high and usually related to the size of the tumour, which may compromise fetal swallowing and subsequently lead to upper airway obstruction. We present a case in which mid-trimester serial sonography demonstrated markedly rapid early growth of a lesion of this type between 17 and 19 weeks' gestation indicating the aggressive nature of this tumour, assisting parental decision to terminate the pregnancy. Histopathology confirmed grade 3 immaturity of the lesion.

Extensive fetal intrathoracic injuries sustained in a motor vehicle accident.

Motor vehicle accidents are the primary nonobstetric cause of maternal and subsequent fetal mortality. We present a case in which blunt abdominal trauma sustained by a pregnant woman in a motor vehicle accident caused extensive intrathoracic fetal injuries consisting of bilateral hemothorax, severe bilateral interstitial pulmonary hemorrhages, hemopericardium, and subepicardial hemorrhages, in addition to fetal cranial injuries. To the best of our knowledge, this is the first report of fetal intrathoracic injuries sustained with blunt maternal trauma. The underlying mechanism of intrathoracic trauma was thought to be similar to that of blast injury with transmission of excessive hydrostatic forces throughout the amniotic fluid with severe impact on the elastic fetal chest. This case supports the concept of in utero blast injury to the fetus as a possible cause for fetal soft tissue trauma associated with blunt trauma to the maternal abdomen.

Absent umbilical artery diastolic flow in a fetus with a partial mole at 18 weeks' gestation.

We present a case in which Doppler velocimetry of the umbilical artery in a fetus with a partial mole at 18 weeks' gestation revealed absent diastolic flow. To the best of our knowledge, this is the first report of Doppler velocimetry of the umbilical artery in this rare condition. Increased placental resistance in this abnormal placenta may explain this finding.

Twin-twin transfusion with abrupt onset of microcephaly in the surviving recipient following spontaneous death of the donor twin.

We describe a case in which twin-twin transfusion with fetal death of the donor at 23 weeks was complicated by suspected intracranial embolic insult of the surviving recipient twin. Dynamic transient intracranial ultrasonographic findings were noted with complete resolution by 28 weeks. Subsequent severe microcephaly of the survivor with no further growth of any of the cranial parameters beyond 25 weeks was thought to be a result of this very unusual pathophysiologic mechanism.