Cynthia Kaplan

Maternal Vascular Underperfusion: Nosology and Reproducibility of Placental Reaction Patterns

Placental examination can be a useful tool for specifying the etiology, prognosis, and recurrence risk of pregnancy disorders. The purpose of this study was to test the reliability of a predetermined set of placental reaction patterns seen with maternal vascular underperfusion in the hope that this might provide a useful diagnostic framework for practicing pathologists. Study cases (14 with clinical and pathologic evidence of maternal underperfusion plus 6 controls) were evaluated for the presence or absence of 11 lesions by eight perinatal pathologists. After analysis of initial results, diagnostic criteria were refined and a second, overlapping set of cases was reviewed. The collective sensitivity, specificity, and efficiency of individual assessments for the 11 lesions relative to the group consensus ranged from 74–93% (22/33 > 90%). Reproducibility was measured by unweighted kappa-values and interpreted as follows: < 0.2 poor, 0.2–0.6 fair/moderate, > 0.6 substantial. Kappa values for lesions affecting villi and the intervillous space were increased syncytial knots (any −0.42, severe −0.50), villous agglutination (0.42), increased intervillous fibrin (0.25), and distal villous hypoplasia (0.57). Individual estimates of percent involvement for syncytial knots, intervillous fibrin, and distal villous hypoplasia were correlated with placental and fetal weight for gestational age. Extent of increased intervillous fibrin showed the strongest correlation with both placental weight (R = −0.64) and fetal weight (R = −0.45). Kappa values for lesions affecting maternal vessels and the implantation site were acute atherosis (0.50), mural hypertrophy of membrane arterioles (0.43), muscularized basal plate arteries (0.48), increased placental site giant cells (0.54), and immature intermediate trophoblast (0.36). Correlation of maternal vessel and implantation site lesions with the clinical diagnosis of preeclampsia showed that excessive placental site giant cells and immature intermediate trophoblast were more sensitive and efficient predictors, whereas atherosis and muscularized basal plate arteries were more specific. Kappa value for a thin umbilical cord, a possible indicator of fetal volume depletion, was 0.61. Reproducibility for a global impression of maternal vascular underperfusion, taking into account all of the above lesions, was moderate (kappa 0.54) and improved after inclusion of additional pathologic and clinical data (kappa 0.68). Adoption of this clearly defined, clinically relevant, and pathologically reproducible terminology could enhance clinicopathologic correlation and provide a more objective framework for future clinical research.

Histological chorioamnionitis and the risk of early intraventricular hemorrhage in infants born ≤28 weeks gestation

OBJECTIVE:To test the hypothesis that histological chorioamnionitis (CA) is not associated with increased risk of early onset intraventricular hemorrhage (IVH).STUDY DESIGN:Clinical data were prospectively collected for 62 consecutive neonates born before 28 weeks of gestation. Placental histology for CA was performed by a pathologist unaware of the head ultrasound scan (HUS) results. The first HUS was obtained by 30 minutes of life. Follow-up HUS were performed before 24 hours and again at 48 to 72 postnatal hours of life. An IVH (grade I to IV) at less than 72 hours of life was deemed an early hemorrhage.RESULTS:Nine of the 62 (14.5%) infants had early onset IVH. In all, 29 infants were born to women with histological evidence of CA; 33 infants did not have CA. Infants did not differ in birth weight, gestational age, sex, cord blood pH, 5-minute Apgar score of <7, cesarean delivery, prenatal use of steroids, administration of tocolytics, need for resuscitation, presence of pneumothorax, platelet count at birth, or use of surfactant. Early IVH rates (3/29 in CA vs 6/33 in non-CA) were similar (p=0.48). Two infants in each group with early IVH died before 2 weeks of age. Five additional infants from the CA group developed IVH at more than 72 postnatal hours of life (late onset IVH), and two of those infants progressed to develop periventricular leukomalacia (PVL). In contrast, only three non-CA infants had late IVH and none developed PVL. Logistic regression confirmed that no perinatal variables including CA were associated with early onset IVH.CONCLUSION:Chorioamnionitis is not associated with increased risk of early IVH.

Pulmonary Agenesis Association with Nonimmune Hydrops

Bilateral pulmonary agenesis is a rare malformation with 13 cases previously reported. To our knowledge, none of these cases have been associated with hydrops fetalis. We report a 36 weeks, hydropic female infant (46XX) with bilateral pulmonary agenesis, unilateral microophthalmia, and bilateral renal dysplasia. These eye and pulmonary findings have now been associated several times and may constitute a new syndrome. Ultrasound examination before delivery showed polyhydramnios and fetal hydrops. At autopsy the heart was structurally normal, aside from absent pulmonary connections. The ductus arteriosus was partially closed. This was felt to be etiologic in the hydrops. As the source of the amniotic fluid here could not be urine or pulmonary secretions, direct fluid transfer from fetal vasculature or skin was the likely origin.

Fibrinogen mRNA and antigen co-present in human trophoblasts in situ: Possible implications

Abstract A unique characteristic of normal human placenta is the presence of “fibrinoid”, a fibrin-rich extracellular deposit in numerous sites (1–5). Fibrinoid is absent from comparable sites of other normal tissues, displays the typical electron microscopic periodicity of fibrin polymers (1), and in addition to fibrin it contains intact fibrinogen (6). The origin of these fibrin/fibrinogen (FA) deposits is uncertain. The intracytoplasmic presence of FA in interstitial (e.g. a commonly known type is intermediate) trophoblasts not residing near villous or other vascular structures (3), however, is inconsistent with a maternal origin of FA in that these cells migrate to the villous surface and differentiate into syncytial trophoblasts (1). The present studies describe the copresence of fibrinogen mRNA and FA in trophoblasts in situ.

Renal Pathology of Prenatally Diagnosed Nephrosis

Congenital Finnish nephrosis is a rare autosomal-recessive disorder, usually fatal at an early age. The disease is prenatally detected through elevation of alpha fetoprotein in the amniotic fluid of pregnancies at risk. This originates from fetal proteinuria. Maternal serum alpha fetoprotein reflects amniotic fluid levels. We describe a case of congenital nephrosis diagnosed through maternal serum screening in a low-risk population. The characteristic histology of congenital nephrosis is demonstrated, and evidence of proteinuria by electron microscopy, light microscopy, and immunofluorescence is presented.

High-resolution imaging diagnosis of human fetal membrane by three-dimensional optical coherence tomography

Microscopic chorionic pseudocyst (MCP) arising in the chorion leave of the human fetal membrane (FM) is a clinical precursor for preeclampsia which may progress to fatal medical conditions (e.g., abortion) if left untreated. To examine the utility of three-dimensional (3D) optical coherence tomography (OCT) for noninvasive delineation of the morphology of human fetal membranes and early clinical detection of MCP, 60 human FM specimens were acquired from 10 different subjects undergoing term cesarean delivery for an ex vivo feasibility study. Our results showed that OCT was able to identify the four-layer architectures of human FMs consisting of high-scattering decidua vera (DV, average thickness d(DV) ≈ 92±38 μm), low-scattering chorion and trophoblast (CT, d(CT) ≈ 150±67 μm), high-scattering subepithelial amnion (A, d(A) ≈ 95±36 μm), and low-scattering epithelium (E, d(E) ≈ 29±8 μm). Importantly, 3D OCT was able to instantaneously detect MCPs (low scattering due to edema, fluid buildup, vasodilatation) and track (staging) their thicknesses d(MCP) ranging from 24 to 615 μm. It was also shown that high-frequency ultrasound was able to compliment OCT for detecting more advanced thicker MCPs (e.g., d(MCP)>615 μm) because of its increased imaging depth.

Intact newborn survival after spontaneous umbilical cord vascular rupture before labor.

BACKGROUND: Spontaneous umbilical cord vascular rupture is a rare event and historically has led to rapid neonatal demise. This catastrophic event has a small window of opportunity in which intervention may prevent neonatal death. CASE: A 32-year-old multigravid womans prenatal care was complicated by fetal anomalies, including a two-vessel cord and right pelvic kidney diagnosed during second-trimester ultrasonography. The patient had undergone weekly antenatal testing that was reassuring. She presented to labor and delivery at 36 weeks of gestation with decreased fetal movement and fetal tachycardia and urgently underwent cesarean delivery. On delivery, avulsion of the umbilical cord was noted. The neonate was resuscitated by the neonatal intensive care team and was discharged from the hospital on day of life 14. CONCLUSION: A high clinical suspicion of potential prelabor cord avulsion and rapid intervention can lead to the birth of a live newborn.

Collagen expression in the pregnant human cervix is decreased with labor.

Objective The current study tested the hypothesis that collagen content in the pregnant cervix decreases with labor, using morphologically preserved specimens, avoiding limitations of earlier studies. Collagen abundance remote from pregnancy was also evaluated. Materials and Methods Histologic sections of postpartum cervix obtained from 22 cases of total hysterectomy performed immediately after delivery: 13 cases performed after delivery with no labor and 9 cases in which labor had ensued before delivery. Cervices from 10 nonpregnant uteri served as additional controls. Sections were stained, and quantitative histomorphometric assessment of relative collagen abundance was performed using computer-assisted image analysis. Data were assessed for differences using rank sum tests. Relationships between cervical collagen abundance and age, parity, ethnicity, or mode of delivery were also assessed. Results Quantitative assessment of collagen abundance in trichrome-stained cervical sections revealed significantly decreased cervical collagen expression in sections from pregnant uteri. Mean percent collagen was 73.5% ± 3.5% (±SEM) in cervices from nonpregnant uteri (n = 10) and 21.5% ± 2.2% in cervices from pregnant uteri (n = 22, p < .0001). Cervical collagen content was significantly lower (p = .04) in cervices from cases in which labor had ensued before delivery (mean percent collagen = 16.1% ± 3.4%, n = 9) than in those in which delivery occurred with no labor (25.3% ± 2.3%, n = 13). No relationships between collagen expression and age, parity, ethnicity, or mode of delivery were observed. Conclusions Collagen expression seems to be reduced in the postpartum cervix, particularly after labor has ensued.

Isolated Placental Inflammation and Vasculopathy: Clinical Implications in the Extremely Low Birth Weight Infants

ABSTRACT The predictive values of placental histopathologies are compromised by a non-segregation of common anomalies. The effects of isolated pure placental inflammation (PI) and vasculopathy-coagulopathy (PV) were compared with normal (NL) placentas in extremely premature infants (ELBW, birth weight < 1000 g). PI infants required lower peak inspiratory pressure on day 3. More infants in PV were oxygen dependence on day 28. PV had an increased risk of intraventricular–periventricular hemorrhage (IVH, OR 4.9, 95% CI 1–24.7, p = 0.05). NL infants were unexposed to PPROM or maternal hypertension, had highest requirement for surfactant, did not develop IVH and periventricular leukomalacia (PVL) and none of them were Caucasian. Conclusions: In ELBW infants (1) pure placental vasculopathy-coagulopathy is a risk factor for IVH, (2) a non- pathological intrauterine environment is nonconducive to IVH and PVL, (3) pure placental inflammation is protective for acute pulmonary disease, (4) Caucasian mothers are more susceptible to adverse intrauterine environment.

Handling of Perinatal Specimens: A Society for Pediatric Pathology Practice Committee Survey

Despite published recommendations [1–3], there is wide variation in the handling of perinatal specimens. The importance of the examination of the fetus and placenta in stillbirth cases has been stressed by The American College of Obstetricians and Gynecologists [4]. A 33-question survey in this regard was e-mailed to all 598 Society for Pediatric Pathology members. Fifty-one (8.5%) anonymous surveys were returned. It is likely, based on numbers of attendees at the symposia and meetings of the Perinatal Section of the SPP, that these individuals composed the majority of the survey respondents. Percent of workload and number of cases represented by placentas was variable. Forty-six respondents (94%) reported that .30% of received placentas were from thirdtrimester fetuses. Twenty-nine respondents (69%) reported they receive fresh placentas. Storage was extremely variable. Seven respondents (15%) receive placentas from all deliveries, 11 (23%) receive placentas from cases that are considered problems by the obstetricians, 1 (2%) receives placentas from cesarean section cases and cases the obstetricians consider problems, 2 (4%) receive placentas from cases on neonatology request, 9 (19%) receive placentas based on College of American Pathologists protocol (3), 3 (6%) receive them based on internal pathology protocol, and 1 (2%) on a combination of internal pathology and College of American Pathologists protocols. Not all questions were answered by all respondents, so the denominator varies for different questions. The number of fetal surgical specimens and fetal autopsy specimens received was extremely variable. To separate examinations into surgical accessions versus full autopsies, 14 respondents (30%) reported that they followed hospital policy, 18 (38%) followed state regulations, 5 (11%) followed a combination of hospital and state regulations, 1 (2%) used a cutoff of 11 weeks of gestational age (GA), 1 (2%) used a cutoff of 16 weeks, 1 (2%) used New York City regulations, 5 (11%) considered all intact fetuses as autopsies regardless of GA, 1 (2%) reported following a combination of pathology department plus hospital policy, and 1 (2%) based the decision on pathology departmental policy. Twenty-three respondents (53%) used a cutoff of 20 weeks GA, 4 (9%) used a cutoff of .24 weeks, 3 (7%) used weight .500 g as a cutoff, 1 (2%) reported the cutoff as 20 weeks or 500 g, 1 (2%) used a cutoff .250 g, 1 (2%) used a cutoff of 20 weeks or any Apgar score, 1 (2%) used weight of 1500 g or live delivery, 5 (11%) said all were autopsies, regardless of parameters, 3 (7%) used a cutoff of 20 weeks or 350 g, 1 (2%) used a cutoff of .11 weeks GA, and 1 (2%) used a cutoff of .16 weeks GA. For fetuses classified as surgical specimens, 7 respondents (15%) do not require consent, 14 (30%) examine all fetuses unless an objection is raised, and 18 (39%) require a consent regardless of GA. Individual answers (2% each) included gross examination only, written consent required if 20 weeks GA, otherwise verbal consent required, ‘‘prefer consent,’’ 14 weeks inhouse cases require consent and 20 weeks require consent if a consult; all are handled as autopsies, .1500 g requires consent while ,1500 g varies, and consent is needed for 16 weeks GA. If clinical dating is poor, 12 respondents (27%) use foot length, with cutoffs variable, including 3.0, 3.2, 3.4, and 3.5 cm. Nine respondents (20%) rely on weight, 15 (33%) on stated GA, and 3 (7%) stated that all cases were handled as autopsies. Individual answers (2% each) included stated age or .500 g, ponderal index, judgment, a combination of foot length, weight and stated GA; and a combination of foot length, weight, and crown heel .8 cm. Experience was extremely variable, with various combinations of fellowship-trained pediatric pathologists, non–fellowship-trained pediatric pathologists, perinatal pathologists, gynecologic pathologists, general surgical pathologists, and autopsy pathologists handling perinatal specimens. For evaluating nonlesional placentas, 5 respondents (10%) submit 2 sections; 13 (27%) reported 3, 17 (35%) Pediatric and Developmental Pathology 12, 307–308, 2009