Investigation of nonimmune hydrops fetalis: multidisciplinary studies are necessary for diagnosis--review of 94 cases.

This review of 94 cases of nonimmune hydrops fetalis (NIHF) over a 10-year period was undertaken to evaluate the frequency of this pathology among fetal and infant deaths and to determine the most common likely etiologies in a northeastern region of France. NIHF represented 6% of the fetal deaths examined in our laboratory. The combination of findings from morphologic examination of the placenta and fetus with the results of microbiological and cytogenetic investigations (conventional cytogenetic study, fluorescent in situ hybridization [FISH], or DNA ploidy image analysis) led to an etiologic diagnosis for NIHF in two-thirds of the cases and suggested a diagnosis in an additional 23% of cases. The most common causes of NIHF were chromosome abnormalities (33%), infections (16%), and cardiac pathology (13.8%). The detection of a cause for NIHF is important for genetic counseling and management of subsequent pregnancies. Our experience suggests that a diagnosis is possible in a large majority of NIHF when obstetricians and pathologists carefully coordinate the management of prenatal and postnatal investigations and when new techniques, such as molecular biology and DNA quantification, are used.

In vivo localization of the insulin-like growth factors I and II (IGF I and IGF II) gene expression during human lung development.

The insulin-like growth factors I and II (IGF I and IGF II) are synthesized in many organs during human development and are involved in the growth and differentiation of tissues. Correlations between lung growth and maturation and the local production of IGFs have been poorly explored in humans. Using in situ hybridization we localized the synthesis of IGFs in the human fetal respiratory tract over an extended period of the gestation and we demonstrated time dependent changes. IGF mRNAs were expressed throughout gestation with a clear predominance of IGF II and a decreasing expression of both IGFs after the 20th week of gestation. They were mainly detected in the mesodermal-derived components of the respiratory tract, especially in the undifferentiated mesenchyme of the lung buds up to 20 weeks of gestation. At this time the local production of collagen and the proliferation of adjacent epithelial cells were predominant features. Later, mesenchymal hybridization decreased. Weak epithelial hybridization was observed during the first stages of growth and progressively decreased when the epithelium underwent maturation: early in the trachea, later in the distal lung buds. A consistent expression of IGF II, but not IGF I, in the endothelium, throughout gestation, was also observed. The IGFs may act on the near epithelial cell proliferation in both autocrine and paracrine ways. They may also stimulate the maturation of the connective tissue. This endogenous production of growth factors may play a role in the somatic growth during prenatal life.

Synthesis and expression of laminin during human foetal lung development.

BACKGROUND: The lung develops by epithelial tubes budding and branching into a flexible mesenchyme. This growth is associated with the remodelling of the epithelial basement membrane, of which laminin is a major component. METHODS: Both the synthesis and expression of laminin were studied in the human lung between 10 and 31 weeks of gestation, using in situ hybridization and immunohistochemistry. RESULTS: The synthesis of the beta chain was active in the epithelial and surrounding mesenchymal cells. The mRNAs coding for the gamma chain were less abundant and mainly found in the epithelium. The synthesis of these two chains continued throughout gestation, and no significant difference in the density of hybridization grains could be detected between the tips of the expanding buds and the proximal portions. Immunohistochemical localization of laminin showed important modifications of the basement membrane during gestation. In the first part of the pseudoglandular stage the epithelial basement membrane stained continuously for laminin. Later, the basement membrane was labelled in a graded fashion: at the apex of the growing buds the staining became weak with focal disruptions. Both epithelial and mesenchymal synthesis of laminin remained active, while the polypeptide was undetectable using immunohistochemistry. CONCLUSIONS: These findings suggest that the remodelling of the basement membrane during human lung morphogenesis is probably not related to a decreasing synthesis of laminin, but to either a proteolytic degradation or the assembly of an inadequate complex undetectable with the polyclonal antibody antilaminin.

Spontaneous abortions during the second trimester of gestation.

To determine the factors causing spontaneous abortions, 422 consecutive second-trimester abortions and the corresponding clinical data were studied prospectively. All of the fetuses and placentas were referred to a single pathologist and microbiological cultures were carried out in 205 of these cases. One hundred twenty-one medically included abortions were used as controls for the interpretation of the investigations relating to infection. According to the degree of maceration, two groups could be isolated and seemed to represent different diseases and mechanisms of spontaneous abortions. In the largest group (78.6%) without long intrauterine retention, one explanation could be given for 85% of these cases. Ascending infections occurred through unruptured membranes, whether or not they were associated with obstetric complications. The second group (21.4%) included severely macerated fetuses where a cause of death could only be determined in 44% of the cases that had a predominance of fetal abnormalities and maternal factors.

Expression and immunohistochemical localization of laminin and type IV collagen in developing human fetal tracheal glands.

The expression and distribution of laminin and type IV collagen, two major components of the basement membrane, were investigated at the epithelio-mesenchymal interface of the human developing tracheal glands from 10 to 37 weeks of gestation. The localization of these molecules was assessed by indirect immunoperoxidase and indirect immunofluorescence staining and correlated to morphogenesis and epithelial cell differentiation. Laminin and type IV collagen were detected as early as 10 weeks of gestation in a continuous, linear pattern in the basement membrane surrounding the epithelial tracheal tube. By 12 weeks of gestation the basement membrane developed large openings at the tips of the budding glands beneath poorly differentiated cells, concomitant with the onset of morphogenetic movements. The remodeling of the basement membrane led to branching epithelial morphogenesis. The maturation and the functional differentiation of the secretory cells appeared later in the epithelium, when the basement membrane was strongly labeled with both anti-laminin and anti-type IV collagen antibodies, after 24 weeks of gestation. At this time the basement membrane became regular and thick and the maturation of serous cells increased progressively. These results suggest that the remodeling of the basement membrane takes place very early during gestation and that the morphogenesis and the maturation of the tracheal glands are rapidly achieved in humans.

Fetal listeriosis during the second trimester of gestation.

Listeriosis is common and is implicated in about 3% of second-term abortions examined in our laboratory. Maternal fever was followed rapidly in all instances by the expulsion of a nonmacerated fetus. Chorioamnionitis was always present and was associated with placental microabscesses. Leukocytic infiltrates were frequent in fetal tissues, being present in adrenal, lung, and skin. Listeria monocytogenes was isolated from 8 of the 205 abortions that had microbiological cultures (3.9%). The clinical features and morphological lesions were so characteristic that the diagnosis of listeriosis could be made in 5 of the 217 fixed abortuses received during the same period, but without culture. In contrast to the third trimester of pregnancy, there were no inflammatory lesions in the central nervous system in our small series.

Fetal adrenal development during the second trimester of gestation.

Four hundred and fifty pairs of adrenals were studied from human fetuses ranging in age from 15 to 27 weeks of gestation (menstrual age). They were collected from spontaneous and medical abortions. The adrenal weight increased from 0.2 to 1.5 g during the second trimester. The left adrenal was significantly heavier than the right for the same gestational age. The length (L1), the height (L2) and the thickness (L3) of the adrenals were measured. The index of length (L1 x L2 x L3) correlated well with the fetal age, except for the Potter Syndrome in which it was decreased. This index could be a useful indicator for ultrasonographic and pathologic studies of the fetal adrenal gland. The cells of the fetal cortex contained lipid droplets during the first weeks of the mid-trimester, and this storage progressively decreased after 20-21 weeks. The fatty transformation that is used as an indicator of the mode of death of stillborn infants cannot be applied to abortions during the second trimester. In a few instances, hypoxia was associated with adrenal hypertrophy.