Does the presence of placental basal plate myometrial fibres increase the risk of subsequent morbidly adherent placenta: a case-control study.

OBJECTIVE: Antenatal diagnosis of morbidly adherent placenta has been shown to improve outcomes, but existing predictors lack sensitivity. Our objective was to determine whether the presence of myometrial fibres attached to the placental basal plate (BPMYO) in an antecedent pregnancy is associated with subsequent morbidly adherent placenta. DESIGN: A case-control study. SETTING: Departments of Obstetrics and Gynecology and Pathology, Northwestern University, Chicago, IL, USA. SAMPLE: Women who had at least two pregnancies with placental pathological evaluation. METHODS: Cases were defined as women with evidence of morbidly adherent placenta (both clinically and pathologically) in their most recent pregnancy whereas women without evidence of morbidly adherent placenta served as controls. Pathological specimens of placentas from previous pregnancies were evaluated for BPMYO. The presence of BPMYO on a previous placenta was evaluated to determine whether it could be used to improve the antenatal diagnosis of morbidly adherent placenta. RESULTS: Of the 25 cases of morbidly adherent placenta, 19 (76%) had BPMYO present on their previous placenta compared with 41 (41%) of controls (odds ratio 4.8, 95% CI 1.8-13.0). Adding BPMYO to a regression including other risk factors for morbidly adherent placenta (i.e. maternal age, number of previous caesarean sections, placenta praevia, previous multiple gestation, any previous curettage, and ultrasonographic suspicion of placenta accreta) significantly improved the sensitivity of antenatal diagnosis of morbidly adherent placenta (61% versus 39%, P < 0.001) without a change in specificity (97% versus 97%, P = 1.00). CONCLUSION: BPMYO on previous placental pathology is associated with an increased risk of morbidly adherent placenta in a subsequent pregnancy. These findings may shed light on the pathophysiology of accreta and inform future research on predictors of accreta. TWEETABLE ABSTRACT: Previous basal plate myometrium improves the ability to detect subsequent morbidly adherent placenta.

Stillbirth: Genome-wide copy number variation profiling in archived placental umbilical cord samples with pathologic and clinical correlation.

INTRODUCTION: Stillbirth remains a devastating health issue with 26,000 stillbirths occurring annually in the United States. Formalin-fixed, paraffin-embedded (FFPE) umbilical cord samples are available for many stillbirths. Our aim was to validate the use of these samples in identifying genetic variations in stillbirth through microarray analysis. METHODS: This is a retrospective case-control study from a single institution of stillbirths ≥ 23 weeks gestational age and control liveborn infants. Fetal genomic DNA was extracted from FFPE umbilical cord samples of stillborn and control placentas, and genotyping was performed using the Illumina HumanOmniExpresss-12v1 Beadchip. Array results were verified with qPCR. RESULTS: 31 case-specific CNVs (17 deletions and 14 amplifications) with an average size of 294 kb for amplifications and 74 kb for deletions were identified among 94 FFPE samples (86 cases; 8 controls). In total 38 (44%) of the stillbirth samples had a CNV detected. Validation of a subset of microarray findings with qPCR confirmed deletions on 1p (2 cases), 11q (4 cases) and amplifications on 18 (1 case). Placental underperfusion changes were seen in stillborns with deletions on 1p, a region containing complement regulatory genes which have been shown to play a role in preeclampsia. DISCUSSION: This study validated the use of archived FFPE umbilical cord samples for genome-wide copy number profiling in stillbirths, and demonstrates specific CNV deletions and amplifications. Microarray analysis in an expanded cohort of stillbirth FFPE samples has the potential to identify biomarkers involved in stillbirth pathogenesis.

Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH. METHODS: We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates. RESULTS: Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P < 0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio = 2.6; 95% confidence interval = 1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P < 0.001). DISCUSSION: Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease. CONCLUSIONS: Our findings have important implications for providing earlier and more effective therapies for BPD.

Gross patterns of umbilical cord coiling: correlations with placental histology and stillbirth.

INTRODUCTION: The purpose of this study was to define gross patterns of umbilical cord hypercoiling and determine correlations with histological features in the placenta and/or perinatal outcomes such as stillbirth. METHODS: Gross images of placentas with hypercoiled umbilical cords (>3 coils/10 cm) were assigned a major umbilical coiling pattern and the direction (right or left) of the coiling. Definitions of 4 gross coiling patterns were established: undulating, rope, segmented, and linked, each with progressively deeper indentations in cord diameter. Outcome variables obtained from placental pathology reports and maternal medical records included histological abnormalities indicative of significant chronic fetal vascular obstruction, such as fetal vascular thrombi, avascular villi, villous stromal-vascular karyorrhexis, and fetal thrombotic vasculopathy, and stillbirth. RESULTS: 318 placentas/umbilical cords met inclusion criteria. The rope pattern was the most common (52%), followed by the undulating (26%), segmented (19%) and linked (3%) patterns. The segmented and linked gross coiling patterns were significantly correlated with histologic evidence of chronic fetal vascular obstruction and stillbirth, when compared with the ropeand undulating patterns. Cords with right twists were also significantly correlated with histologic evidence of chronic fetal vascular obstruction and stillbirth when compared with cords with left twists. The number of cord coils per 10 cm did not correlate with any of the outcome variables. CONCLUSIONS: Among hypercoiled umbilical cords, specific gross patterns of coiling can be recognized, and patterns with the most significant indentation or pinching of the cord diameter are associated with histological evidence of chronic fetal vascular obstruction and stillbirth.

Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development.

The generation and homeostasis of bone tissue throughout development and maturity is controlled by the carefully balanced processes of bone formation and resorption. Disruption of this balance can give rise to a broad range of skeletal pathologies. Lethal osteosclerotic bone dysplasia (or, Raine syndrome) is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Affected individuals survive only days or weeks. We have identified and defined a chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion in an affected subject. The extent of the deleted region at the 7p telomere was established by genotyping microsatellite markers across the telomeric region. The region is delimited by marker D7S2563 and contains five transcriptional units. Sequence analysis of FAM20C, located within the deleted region, in six additional affected subjects revealed four homozygous mutations and two compound heterozygotes. The identified mutations include four nonsynonymous base changes, all affecting evolutionarily conserved residues, and four splice-site changes that are predicted to have a detrimental effect on splicing. FAM20C is a member of the FAM20 family of secreted proteins, and its mouse orthologue (DMP4) has demonstrated calcium-binding properties; we also show by in situ hybridization its expression profile in mineralizing tissues during development. This study defines the causative role of FAM20C in this lethal osteosclerotic disorder and its crucial role in normal bone development.

Intraplacental smooth muscle tumor: a case report.

We present the second reported case of a smooth muscle neoplasm involving the placental parenchyma. On gross examination, the tumor easily separated from the uterus and had a whorled cut surface with finger-like extensions into the villous parenchyma, very similar to the previously described case. The differential diagnosis included a primary smooth muscle tumor of the placenta (placental leiomyoma), a primary uterine neoplasm incorporated into the placenta, and a metastatic sarcoma. In this case, the infant was male, and the polymerase chain reaction technique demonstrated the presence of Y chromosome gene in the placental parenchyma and its absence in the placental neoplasm. Thus, this neoplasm, despite its gross appearance of a primary placental tumor, actually represented an incorporated benign uterine leiomyoma.

Cell populations in the bone marrow of guinea pig fetuses with intrauterine growth retardation.

Bone marrow smears and blood samples were examined in guinea pig fetuses in which intrauterine growth retardation (IUGR) had been induced by uterine artery ligation and compared with those of control (well-grown) fetuses from uterine horns with intact circulation. Differential bone marrow cell counts were obtained from a count of 300 cells per smear and blood samples were assayed for hemoglobin concentration and 2,3-diphosphoglycerate (DPG). Results of blood assays showed no difference in hemoglobin concentration. DPG levels were reduced in the IUGR guinea pigs (P < .05), which could be a consequence of decreased glucose availability or represent an adaptation to reduced oxygen availability. Comparisons of bone marrow counts revealed an increase in total erythrocyte precursors (P < .05) and a decrease in total granulocytic precursors (P < .05) in IUGR fetuses. Within the erythroid lineage there was a significant increase in late (orthochromatic) erythroblasts (P < .005) in the IUGR animals compared with control animals. The granulocytic lineage of the IUGR fetuses showed a significant decrease in mature neutrophils (P < .05) and eosinophilic precursors (P < .05) compared with controls. These data suggest that the hypoxic stress of uterine artery ligation leads to an increase in medullary erythropoiesis. In concert with a previous study that showed a reduction in hepatic erythropoiesis, these data suggest a precocious shift of the anatomic site of erythropoiesis from the liver to the bone marrow under conditions of hypoxia.

Hepatic histology in intrauterine growth retardation following uterine artery ligation in the guinea pig.

Hepatic histology was examined in guinea pig fetuses in which intrauterine growth retardation (IUGR) was induced by unilateral uterine artery ligation and compared with that of control (well-grown) fetuses from uterine horns with intact circulations. From all animals, sections taken from the six lobes of the liver were prepared using hematoxylin and eosin stains. Periodic acid-Schiff and Prussian blue stains (both on fixed samples) and Oil Red O stains on frozen tissues were performed on a subset of samples. Comparisons revealed greater fat content in hepatocytes (P < .05) and decreased total hepatic hematopoiesis (P < .01) in IUGR animals than in controls. No differences in hepatocyte histology among lobes were observed in control animals. IUGR animals had increased fat content and decreased extramedullary hematopoiesis in the lobes receiving the portal circulation (P < .05). These data indicate significant abnormalities of hepatic lipid metabolism in IUGR animals following uterine artery ligation. An unexpected and counterintuitive finding was the decrease in hepatic hematopoiesis in the right side of the liver.

The very low birthweight infant: maternal complications leading to preterm birth, placental lesions, and intrauterine growth.

The placental lesions of the very low birthweight (VLBW) infant were investigated in relation to clinical complications leading to preterm birth and evidence of growth impairment. The 249 singleton gestations yielding infants less than 1500 g were grouped according to the clinical complications leading to preterm birth as premature membrane rupture (116/249, 47%) preterm labor (55/249, 22%), pregnancy-induced hypertension (PIH, 54/249, 22%), and normotensive abruption (ABR, 24/249, 10%). Specifically excluded from this data set were cases with greater than 2 weeks discordance, fetal congenital anomalies, placenta previa, and maternal medical or gestational diseases such as chronic hypertension and diabetes mellitus, and intrauterine growth retardation (IUGR) as a primary indication for delivery. Placental weight and lesions including decidual vasculopathy and related villous lesions, chronic villitis/intervillositis, and decidual plasmacytosis were considered as variables in analyses in which raw birthweight was the dependent variable and gestational age a confounder. Of the 195 VLBW, 79 (41%) infants from normotensive mothers had lesions of decidual vasculopathy or chronic inflammation. In the VLBW infants from hypertensive mothers, growth restriction was related to markers of decidual vasculopathy. In the absence of maternal hypertension the growth restriction was independently associated with chronic villitis. Decidual vasculopathy (characteristic of PIH) and chronic intrauterine inflammation underlie the complications of many normotensive VLBW infants. The placental lesions in VLBW-IUGR depend on the presence or absence of maternal hypertension. In the absence of maternal hypertension, VLBW-IUGR is associated with chronic inflammation and is independent of decidual vasculopathy. In the presence of maternal hypertension, VLBW-IUGR is directly related to decidual vasculopathy.