A Perinatal Pathology View of Preterm Labor

In This Article

Placental Pathology and Case Studies 1 and 2

Case 1

The placentas of both pregnancies of Case 1 were reviewed. The first placenta showed severe umbilical cord inflammation with extensive fetal neutrophil karyorrhexis (Figures 1 and 2), although the maternal inflammatory response (as assessed in amnion, chorion and decidua of the extraplacental membranes, and the chorionic plate) was entirely absent (Figure 3). Special stains showed numerous colonies of gram-positive organisms, suggestive of streptococcus (Figure 4). The delivery to fixation interval for histologic analysis was less than 12 hours. The second placenta showed focal mild acute deciduitis (Figure 5) and dense chorionic (fetal) vasculitis (Figure 6). Special stains again showed numerous gram-positive cocci within a noninflamed amnion. Maternal and fetal cultures showed heavy growth of group B streptococcus (GBS). The mother had subsequently been recolonized after peripartum antibiotic therapy had eradicated the maternal GBS infection observed during the first pregnancy.

Figure 1.

In this low-magnification view (4x), the inflammatory cells/neutrophils appear as a dark blue haze against the pale pink of the normal Wharton's jelly (substance of the umbilical cord).

Figure 2.

Higher magnification, showing individual dark blue nuclei of inflammatory cells.

Figure 3.

In this low-power view of the membranes (4x), no inflammatory cells are present. The amnion (single arrow) is the inner lining of the membranes. The double arrows mark the junction of the cellular layer of the chorion and the connective tissue layer of the chorion. To the right and below the double arrows is the decidua, the only part of the membranes with blood vessels. When an amniotic fluid infection is present, inflammatory chemicals diffuse across the membranes forming a gradient of chemical attraction. The decidua is a maternal tissue; mother's neutrophils circulating in the decidual blood vessels sense these chemicals and respond by leaving the circulation and entering the tissues. They often "pile up" at the junction of cells and connective tissue in the chorion. No maternal inflammation is present in this view.

Figure 4.

In this view, a tissue Gram's stain highlights innumerable small round blue-staining (gram-positive) microorganisms in chains and clusters. Although definitive identification of microorganism type requires culture, this picture is consistent with streptococcus.

Figure 5.

In this high-magnification view, there is a small focus of cell death with fragments of dark blue nuclear debris and few better preserved acute inflammatory cells (arrows). This pattern would not be specific for infection; it is focal, with few neutrophils, and would be common in the site at which the membranes had ruptured spontaneously.

Figure 6.

The fetal blood vessel (arrow) is the source for fetal acute inflammatory cells that are too numerous to count. The amniotic fluid space would be at the upper edge of the picture; the small dark blue nuclei of fetal inflammatory cells are dense at the margin of the blood vessel wall and pepper the full thickness of the pale pink connective tissue of the chorionic plate.

Case 1 exemplifies the recurrent nature of acute ascending infection and also the unique histopathology that is common in catastrophic intrapartum or peripartum GBS infections. When bacteria can be implicated in the genesis of preterm birth, repetitive obstetric complications from "incompetent cervix" to spontaneous prematurity may share the same histopathology even over a decade or more of reproductive life. Because the "bacterial vaginosis" group of organisms has been associated with clinical symptoms even in menopausal women, the possibility that long-standing bacterial flora may complicate the reproductive years is by no means a surprise.

Pandey and colleagues[16] showed that differences in the ability to mount immune responses to GBS antigens is at least in part genetically determined. Because of the comparative immune incompetence of the fetus, finding a well-established fetal inflammatory response given no such maternal response is uncommon. A newborn is more susceptible to infection than an adult or even a young child. The more preterm the fetus, the greater the disparity ought to be between the response of the fetus to inflammatory stimuli in the amniotic fluid space and the response of the mother to that same stimulus. When the fetal response is greater, it is abnormal. In the absence of a clinically recognizable response in the mother, pathologic determination of a severe fetal inflammatory response should warrant special care and prophylactic treatment in subsequent pregnancies.

Case 2

After the patient's first loss, she requested a second opinion regarding the placental diagnosis. Review by a second pathologist specializing in obstetric pathology resulted in a diagnosis of extensive ischemic necrosis of the membranes, with no evidence of infection (Figure 7). Maternal blood vessels showed reduced caliber and changes within the blood vessel of chronic inflammation and injury (Figure 8). The placenta showed fibrosis and "scarring" of villi, with large clumps of fibrin/fibrinoid between villi. (Figure 9). After these diagnoses, additional blood studies were recommended because of the observed vascular changes and a family history that suggested heritable thrombophilia. The evidence in support of heritable thrombophilia in association with recurrent pregnancy loss and uteroplacental vascular complications remains controversial. It remains to be seen whether a strong family history of premature cardiovascular sequelae and a personal history of uteroplacental vascular abnormalities calls for a complete genetic thrombophilia work-up, especially because we may be aware of only a small percentage of the polymorphisms that may contribute to an abnormal vascular environment.

Figure 7.

In this low-magnification view, a well-formed clot of maternal blood (arrow) and necrotic ghost villi (double arrows) are seen. In neighboring sections, this clot was associated with death of the decidua of the basal plate; this constellation of findings is consistent with a hemorrhagic maternal vascular accident, or abruption. A maternal blood vessel, often following thrombosis, breaks open and bleeds behind the placenta. This blood destroys the basal plate, which anchors the placenta to the uterine lining. Maternal blood between the villi forces the villi apart and forms a clot, with villi entrapped within the clot undergoing necrosis.

Figure 8.

This high-magnification view shows the wall of a maternal blood vessel with a fibrinoid (acellular and pink) wall within which are embedded fetal trophoblasts (double arrows). Internal to this wall should be only a single-cell layer of delicate endothelium. Instead, there are spindle-shaped myofibroblast nuclei (arrows) with scattered round, dark blue nuclei of lymphocytes, indicating chronic inflammation. The myofibroblast response is, in other blood vessels, a common pattern of blood vessel response to injury.

Figure 9.

The perivillous fibrin/fibrinoid (arrows) is abnormally prominent in this extremely preterm placenta. These large areas of material occasionally completely surround villi; such villi would not be able to exchange nutrients with the maternal blood (the white areas in this picture). Fibrinoid necrosis has been shown to be an essential part of placental repair after injury.

In light of the current lack of conclusive evidence, her physician stated that the only treatment that would be prescribed in a next pregnancy would be aspirin, regardless of the outcome of comparatively expensive blood tests. (The physician opted not to order them.) Her second pregnancy, in which she took 1 baby aspirin daily, was also sent for detailed pathology review. Again, ischemic necrosis of the membranes and maternal vessel thrombi and narrowing were seen. Her third pregnancy is currently being treated with heparin and followed by uterine artery Doppler blood flow studies; it was progressing well at 22 weeks. She spontaneously abrupted at 28 weeks, delivering a 2 pound 6 ounce newborn who is doing well in the intensive care unit. Given the incomplete understanding of both the source and progression of cardiovascular disease in adults, documentation of abnormal anatomy by placental histopathology may be one of the only early markers of future vascular complications not necessarily limited to pregnancy.


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