Chorioamnionitis, not epidural analgesia, is associated with maternal fever during labour.

PURPOSE: Maternal fever is associated with chorioamnionitis and has been linked to labour epidural analgesia (LEA). The purpose of this study was to determine possible associations between LEA and chorioamnionitis, maternal fever, operative delivery rate, and neonatal outcome. METHODS: Data from 14,073 patients were entered into a database over a two-year period. From this database, 62 nulliparous parturients with clinical chorioamnionitis (amnionitis), but without LEA were identified (Group I). Two other groups who received LEA were matched for parity and gestation: Group II - LEA with concomitant amnionitis (n=50) and, Group III - LEA without concomitant amnionitis (n=201). The diagnosis of chorioamnionitis was confirmed by histologic examination. Results are expressed as mean +/- SD and analyzed at P <0.05 using ANOVA or Chi-square. RESULTS: No differences were noted among the groups in the operative delivery rate or Apgar scores at five minutes. The percentage of patients with maternal fever during labour (38.0 degrees C) with amnionitis was significantly less in Group III compared to the other groups (100% in both Groups I and II vs 1.0% in Group III; P=0.000). Likewise, Group III had a lower percentage of neonates with Apgar scores <7 at one minute (35.5% in Group I, 20.0% in Group II, 17.4% in Group III; P=0.010). The percentage of histologic chorioamnionitis was significantly higher in both amnionitis groups compared to Group III (67.7% in Group I, 56.0% in Group II, 4.0% in Group III; P=0.000). CONCLUSION: LEA without chorioamnionitis is not associated with maternal fever (38.0 degrees C), increased operative delivery rates or low Apgar scores.

Neonates with electrically confirmed seizures and possible placental associations.

Placental specimens were reviewed from 73 singleton pregnancies of women whose offspring received electroencephalogram (EEG) studies in the neonate period. A group of 43 neonates (postconception age [PCA] 23-44 weeks) with electrically confirmed seizures in the immediate neonate period were compared with 30 healthy preterm and term infants of comparable PCA who had no electrographic seizures. Pathologic placental changes were separated: Group A consisted of chorioamnionitis, edema, meconium staining, and/or retroplacental hematoma. Group B consisted of abnormal villous maturation, infarction, and/or chronic villitis. Logistic regression analyses calculated the odds ratio of having Group A or Group B placental lesions in each neonate group as a function of increasing PCA. For the seizure group, the odds of having Group B with or without Group A placental lesions increased by a factor of 1.2 for each postconception week up to 43 weeks PCA. For a 15-week interval the odds of having Group B lesions for the seizure group increased by a factor of 12.1 (P < 0.007). Ratios were not significant for Group A lesions alone in the seizure group or for either Group B or Group A findings in the neonate group without seizures. Pathophysiologic events in utero leading to Group B rather than Group A findings are associated with electrically confirmed seizures in near-term and term infants. Group A lesions were considered more likely to have intrapartum or peripartum associations, whereas Group B lesions were considered more likely to have antepartum associations.

Estimation of hepatic hematopoiesis in second and third trimester singleton gestations using flow cytometric light scatter analysis of archival autopsy tissue.

The purpose of this investigation was to develop a simple, quantitative, reproducible and objective method for estimating fetal hepatic hematopoiesis using flow cytometric light scatter measurements and to use this methodology to determine standard values for singleton gestations. Percent hepatic hematopoiesis was estimated from autopsy tissue both flow cytometrically using forward angle and side light scatter characteristics and histologically (single observer) in 67 s and third trimester singleton gestations without evidence of infection, congenital malformation, chronic maternal or placental disorders, or growth retardation. Correlation of flow cytometric and histologic estimates was 0.70 with flow cytometric estimates showing less variability than histologic estimates, especially during the second trimester. Flow cytometric estimates of hepatic hematopoiesis were relatively constant at 50-70% between 16 and 27 weeks gestational age and decreased during the third trimester to a level of approximately 25-30% at term. These results confirm and quantitate the predicted decrease in hepatic hematopoiesis between the second and third trimesters of gestation as well as its persistence at term. In addition, they demonstrate that flow cytometric light scatter analysis is an objective, valid and simple method for estimating hepatic hematopoiesis in archival autopsy tissue and provides objective standard values for comparison with estimates in pathologic gestations.

Unusual presentations of fetal teratoma.

Teratomas are the most common congenital neoplasm. Fetal intracranial teratomas generally are large solid/cystic tumors that often completely replace normal brain tissue. Mediastinal teratomas are uncommon and rarely result in nonimmune hydrops fetalis. We describe two unusual presentations of fetal teratoma. The first is a fetus with massive hydrocephalus and marked facial deformities that were caused by a small intracranial teratoma. The second is a fetus with a mediastinal teratoma associated with non-immune hydrops fetalis. In both cases, compression by the mass resulted in lethal sequelae.

Low incidence of positive amnionic fluid cultures in preterm labor at 27-32 weeks in the absence of clinical evidence of chorioamnionitis.

In order to determine the utility of amniocentesis for detecting subclinical chorioamnionitis in asymptomatic afebrile women in preterm labor with intact membranes, we enrolled 47 women between 27-32 weeks' gestation in a prospective study. After enrollment, 38 women fulfilled all clinical and laboratory criteria for the study; nine women were excluded because they had a leukocyte count exceeding 15,000/microL. None of the 38 asymptomatic afebrile women had a positive culture from the amnionic fluid for bacteria, fungi, Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, or any viruses. Sepsis was not proved in any of the 38 infants delivered to these patients. There was a clear relationship between histologic evidence of chorioamnionitis and failure of tocolytic therapy. Fetal lung profiles were mature in 29% of the amnionic fluid samples from 30-32 weeks' gestation, but in none of the amnionic fluid samples before 30 weeks. Amniocentesis does not seem useful to detect chorioamnionitis in asymptomatic afebrile women with preterm labor and intact membranes at 27-32 weeks' gestation, and should be reserved for those cases in which information about fetal lung maturity would be helpful.

Morphologic changes in the rat uterus following natural mating and embryo transfer.

In order to gain some insight into the putative immune suppression that may be induced at the placental implantation sites, the morphological changes at these sites following natural matings and following the transfer of embryos fertilized in vivo were studied. The only histologic parameter that showed a significant difference was the number of granulated metrial gland (GMG) cells. More GMG cells were present in allogeneic than in syngeneic pregnancies, and more GMG cells were present following embryo transfer into an allogeneic female than following the comparable natural mating. The role of the GMG cells in pregnancy is, however, still unresolved.

Gene imprinting and major histocompatibility complex class I antigen expression in the rat placenta.

Ultrastructural immunocytochemical studies of the expression of major histocompatibility complex class I antigens in the placentas of inbred rats were performed using placentas derived from natural matings and from embryo transfers into females made pseudopregnant by mechanical stimulation. The studies utilized the WF (u) and DA (a) strains and monoclonal antibodies to all of the class I antigens involved. All four mating combinations of the two strains showed that only paternal antigens were expressed in the placenta and that they were limited to the basal trophoblast. This conclusion was confirmed using embryo transfer experiments. In allogeneic natural matings, the allele-specific class I transplantation antigens were not expressed on the membrane of the basal trophoblast but they were expressed in embryo transfers involving embryos of the same genotype. In both types of pregnancies, the pregnancy-associated (Pa) antigen was present on the membrane of the basal trophoblast. The antibody response to DA X DA and to WF X DA embryos transferred into pseudopregnant WF females was against the allele-specific RT1.Aa antigen and the Pa antigen, whereas the antibody response to the heterozygous embryo in the natural WF (female) X DA (male) mating was against the Pa antigen only. These results are consistent with the hypothesis that the suppression of the expression of the allele-specific major histocompatibility complex class I antigens occurs shortly after fertilization and that it requires the uterine environment of a natural mating.

A unique antigen, RT11, in the placenta of the rat.

In the course of exploring the antibody response in the unsensitized WF (u) female pregnant by a DA (a) male, we prepared a hybridoma that secreted an antibody (mAb 213) that was specific to the a haplotype but identified an antigen different from Pa. This antigen was designated RT11. It is present from the twelfth day of gestation on the collagen fibers of the placenta and of all organs in fetal and adult rats. It is particularly prominent on red blood cells; in the yolk sac epithelium; in the walls of the endodermal sinus, blood vessels and bronchioles; and in capsules and trabeculae. A very small amount is present on DA lymphocytes, since 17-20% of them react with mAb 213 by cytofluorimetry. The RT11 antigen is absent from the basal and labyrinthine trophoblast cells, from the parenchymal cells of all organs, and from T and B cells. This distribution pattern is completely different from that of the Aa and Pa antigens. Inhibition and absorption studies showed that RT11 is not an integral part of the collagen molecule. The SDS-PAGE analysis of the immunoprecipitates of RT11 from radioiodinated whole-membrane extracts of red blood cells and from the glycoprotein fraction thereof showed that it is an unglycosylated protein of molecular weight 29,000. The evidence to date suggests that RT11 is a blood group antigen. Studies on the genetic control of the expression of RT11 were undertaken to determine whether a gene linked to the MHC was involved and whether the control mechanism was unigenic or polygenic. Backcrosses generated using inbred strains--(DA x BN)F1 x DA-- and using complementary congenic strains--(DA.1N x BN.1A) F1 x BN.1A--showed that the expression of RT11 was under polygenic control, and that both an MHC-linked gene (1.2 cM from RT1.Aa) and genes not linked to the MHC are involved. By contrast, the expression of the Pa antigen is under the control of an MHC gene only.

Disseminated granulomatous disease (BCGosis) following chemoimmunotherapy for ovarian carcinoma.

The use of BCG (bacille Calmette Guérin) in conjunction with cytotoxic chemotherapeutic agents has been advocated in patients with ovarian carcinoma. We describe a patient with stage III, grade I, endometrioid carcinoma of the ovary treated with cisplatin, doxorubicin, cyclophosphamide, and BCG. Following one course of therapy she presented with an elevated temperature, purpuric skin rash, abnormal liver function tests and hematological indices, and multiple organ failure resulting in sepsis and death. At autopsy, disseminated noncaseating granulomas were found in the lungs, hilar lymph nodes, liver, and spleen. Metastatic carcinoma was not present in these organs. This report describes the rapid onset of a disseminated BCG infection (BCGosis) in a patient with ovarian carcinoma receiving chemoimmunotherapy. Clinical recognition of BCGosis in immunocompromised patients is difficult but should be considered in the differential diagnosis of patients presenting with unexplained febrile illness, functional abnormalities in multiple organ systems, and a history of immunotherapy with BCG. Appropriate specimen collection is emphasized.

The clinical significance of hemorrhagic endovasculitis of the placenta.

Hemorrhagic endovasculitis of the placenta has been reported to correlate with intrauterine growth retardation, perinatal morbidity and mortality, and long-term developmental delay. At a regional obstetric hospital we identified 13 cases of hemorrhagic endovasculitis among 1938 placentas from singleton pregnancies of greater than or equal to 20 weeks' gestation over a 3-month period, an incidence of 0.67% of unselected pregnancies. All cases were live-births without intrauterine growth retardation. Associated clinical features were pregnancy-induced hypertension, nuchal cord at delivery, and postterm gestation. One infant had severe perinatal asphyxia with long-term psychomotor retardation. In the placenta, hemorrhagic endovasculitis was associated with infarction, fetal vessel thrombosis, and villitis of unknown cause. Interference with umbilical blood flow or regional compromise of villous perfusion may be an initiating event in the development of this lesion.

Identification, cellular localization, isolation, and characterization of human Clara cell-specific 10 KD protein.

Human lung lavage proteins were fractionated by centrifugation and molecular sieving. An antiserum to the post-albumin fraction of the soluble proteins reacted with a 10 KD protein and this protein was isolated by conventional chromatography. The protein, which has a pI of 4.8, consists of two 5 KD polypeptides and is rich in glutamic acid, leucine, serine, and aspartic acid amino acids. The protein does not bind to concanavalin A, pancreatic elastase, leukocyte elastase, or trypsin, and lacks anti-protease activity. It constitutes about 0.15% of the soluble proteins in lung lavage. Antibodies to the 10 KD protein specifically and exclusively stain Clara cells in human, dog, and rat. Staining of granules of Clara cells was prominent in the distal bronchioles; however, the non-ciliated cells of respiratory bronchioles did not stain for the 10 KD protein. This 10 KD protein appears in fetal lungs at 21 weeks of gestation, and was present in about 10% of the primary pulmonary adenocarcinomas. As a specific marker for Clara cells, this protein could be useful in the study of development, regulation of secretion, and pathobiology of these cells.

Differential expression of MHC class I antigens on the placenta of the rat. A mechanism for the survival of the fetal allograft.

In some mating combinations in rats, there is a maternal antibody response to the maternal antigenic components of the placenta without any previous immunization of the mother. The highest response occurs in the WF (u) female mated to the DA (a) male, and it is against a unique MHC-encoded class I antigen, the Pa antigen, and not against the major allele-specific transplantation antigen of the DA strain, RT1.Aa. The development of mAbs to the Pa and Aa antigens allowed us to localize these antigens on the placenta and to explore the reason for the differential antibody response to them using immunohistochemical and biochemical techniques. Both antibodies reacted with the WF X DA placenta and stained the endovascular and interstitial trophoblast of the decidua, the basal trophoblast, Reichert's membrane, and the yolk sac epithelium, but they did not stain the labyrinthine trophoblast. Blocking studies showed that each antibody reacted with a separate molecule in the placenta. Anti-class II mAbs reactive with the a or u haplotype did not stain the WF X DA, DA X DA, or WF X WF placenta; hence, there are no class II antigens in the placenta. Electron microscopic studies of the semiallogeneic WF X DA placenta using the immunogold technique with both single- and double-labeling showed that only the Pa antigen was expressed on the surface of the basal trophoblast, but that both the Pa and Aa antigens were in the cytoplasm of these cells; neither antigen was found in the labyrinthine trophoblast. By contrast, the placenta from the syngeneic DA X DA mating expressed both the Pa and Aa antigens on the surface of the basal trophoblast as well as in the cytoplasm; neither antigen was found in the labyrinthine trophoblast. These observations were quantified morphometrically using electron photomicrographs of single-labeled tissues. Both the Pa and Aa antigens isolated from the plasma membrane of lymphocytes have heavy chains of 46 kD, but those antigens isolated from the plasma membrane of basal trophoblast cells have heavy chains of 43 kD. Based on densitometric measurements of autoradiographs, the Pa/Aa ratio in the basal trophoblast membrane is 23.5, whereas it is 0.46 in lymphocyte membranes. These studies show that there is differential regulation of the expression of class I antigens on basal trophoblast cells in semiallogeneic pregnancies, but not in syngeneic pregnancies, such that the major allele-specific transplantation antigen is scarcely expressed on the surface of the basal trophoblast.(ABSTRACT TRUNCATED AT 400 WORDS)

Electron microscopic localization of the Pa and RT1.Aa antigens on the placenta of the rat.

A major factor in the ability of the placenta to avoid allograft rejection is the differential expression of MHC class I antigens on its surface. Using monoclonal antibodies and the electron microscopic immunogold technique, we have demonstrated that only the pregnancy-associated (Pa) antigen, which carries a broadly shared antigenic determinant, is expressed on the placental surface in the rat, whereas the allele-specific classical transplantation antigens are not. Both types of antigens are, however, present in the cytoplasm of the basal trophoblast but completely absent from the labyrinthine trophoblast.

Ontogeny of expression of Pa and RT1.Aa antigens on rat placenta and on fetal tissues.

The unique pregnancy-associated (Pa) antigen, which is a class I antigen encoded by the major histocompatibility complex (MHC), elicits a nondestructive maternal antibody response. By contrast, the class I transplantation antigen RT1.Aa elicits a destructive antibody response in tissue transplantation but not during pregnancy. With the use of the avidin-biotin complex (ABC) immunohistochemical method, the Pa and RT1.Aa antigens were localized on the basophilic and giant cells of the basal zone trophoblast, the endovascular trophoblast and decidual interstitial trophoblast, and the chorioallantoic membrane but not on the labyrinthine zone trophoblast as early as the 12th day of gestation. These two antigens were also expressed on the epidermis, hair follicles, spleen, thymic medulla, bronchial epithelium, intestinal epithelium, the hepatic Kupffer cells, endocardium, endothelium of blood vessels, renal tubular cells and glomeruli, and renal pelvis and ureter of fetal and adult rat tissues. Absorption studies with placental tissue confirmed the presence of these two antigens in the rat placenta, and antibody-blocking studies confirmed their unique specificities.

Necrotizing tracheobronchitis in intubated newborns: a complication of assisted ventilation.

This report describes a newly recognized iatrogenic lesion in newborns that we have termed necrotizing tracheobronchitis (NTB). Although it is related to assisted ventilation, it is different from previously described tracheal lesions in that it is most severe distal to the tip of the endotracheal tube and manifests a characteristic basophilic necrosis of the tracheal mucosa. Sloughing of tracheal mucosa, which occurs in the later stages, can cause respiratory obstruction. The lesion occurs over a wide range of gestational ages and birth weights as well as ventilatory rates, pressures, and supplemental oxygen concentrations. The severity of the lesion is related to the duration of ventilation. We believe NTB to be related to airflow through the endotracheal tube rather than to the effects of the tube itself because the lesion is worst beyond the end of the tube and extends into the major bronchi. A grading system is presented.