Rebecca L. Linn

Recurrent massive perivillous fibrin deposition in the placenta associated with fetal renal tubular dysgenesis: case report and literature review.

Massive perivillous fibrin deposition (MPVFD) of the placenta and renal tubular dysgenesis (RTD) are relatively rare diseases with potential recurrent risks that have not previously associated in the literature. Herein, we report the clinical course, autopsy findings, and placental pathologic features from 3 consecutive pregnancies delivered in 1 woman, all showing recurrent MPVFD in the placenta and RTD in the bilateral fetal kidneys.

Adherent basal plate myometrial fibers in the delivered placenta as a risk factor for development of subsequent placenta accreta

BACKGROUND Placenta accreta is implantation of chorionic tissue directly upon the myometrium without normal intervening decidua. The clinical significance of myometrial fibers attached to the basal plate (BPMYO) has yet to be fully elucidated. OBJECTIVE To determine the importance of depth and quantity of BPMYO in predicting subsequent accreta in the next pregnancy. METHOD Women with placentas from two successive pregnancies submitted for pathologic evaluation were included. 50 cases had clinical and/or pathologic diagnosis of accreta in an index pregnancy. 100 controls had no evidence of accreta in an index pregnancy. H&E slides were re-reviewed and stage of accreta/BPMYO was determined. The stages were defined as: Stage 0-no BPMYO; Stage 1-BPMYO with intervening decidua; Stage 2 < 2 decidual cells separating myometrium from chorionic tissue; Stage 3-accreta; Stage 4-increta; Stage 5-percreta. The amount of BPMYO for each placenta was quantified. RESULTS Prior placentas of cases were twice as likely to have BPMYO compared to controls (84%vs42%, P < 0.001). The frequency of stage 1 BPMYO was not significantly different between the two groups (46%v40%, P = 0.489), but cases were more likely to have higher stages of BPMYO (stage 2-3) in a prior placenta (38%vs2%, P < 0.001). A significantly higher number of BPMYO foci and a larger proportion of BPMYO on the basal plate (6.2%vs0.7%, P < 0.001) in cases compared to controls. CONCLUSIONS Small amounts and low stage BPMYO (stage 1) may be common; however, higher stages of BPMYO (stage 2-3) and greater quantities of BPMYO in a delivered placenta are significantly associated with the subsequent development of accreta.

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

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.

Placental Pathologic Associations with Morbidly Adherent Placenta: Potential insights into Pathogenesis.

Background The pathology that underlies morbidly adherent placenta (MAP) is poorly understood. The objective of this study was to describe the placental pathology, especially implantation site pathology, associated with MAP. Methods This was a single institution, retrospective case-control study design examining placentas of patients who delivered between January 2008 and September 2013. MAP cases were defined by the need for clinical intervention at delivery beyond spontaneous placental delivery or simple manual extraction of the placenta. Controls consisted of patients with placentas sent for examination due to a history of maternal malignancy with no clinical suspicion of accreta. Placental pathologic findings of maternal vascular underperfusion (MVU), acute inflammation, chronic inflammation, fetal vascular obstruction, and hemorrhage were recorded and compared using bivariable and multivariable analyses. Results Three categories of pathologic changes were seen more commonly in MAP placentas (N = 101) than control placentas (N = 110): chronic basal inflammation, villous changes of MVU, and retromembranous and subchorionic/intervillous hemorrhage. In multivariable analyses adjusted for confounders, basal chronic villitis (aOR 5.6, 1.73–18.18), plasma cell deciduitis (aOR 2.63, 1.08–6.39), increased syncytial knots (aOR 3.92, 1.57–9.75), villous agglutination (aOR 24.85, 2.78–221.75), increased perivillous fibrin (aOR 5.08, 1.49–17.34), and the presence of subchorionic/intervillous thrombi (aOR 4.01, 1.63–9.86) remained associated with MAP. Conclusions MAP is highly associated with evidence of intraparenchymal placental hemorrhage, villous changes of MVU, and a lymphoplasmacytic infiltrate at the implantation site. The contribution of this basal chronic inflammatory infiltrate to MAP requires further investigation.

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.

pH-neutralizing esophageal irrigations as a novel mitigation strategy for button battery injury: Esophageal Irrigations for BB Injury

Ingestion of button batteries (BB) can rapidly lead to caustic esophageal injury in infants and children, resulting in significant morbidity and mortality. To identify novel mitigation strategies, we tested common weakly acidic household beverages, viscous liquids, and Carafate® for their ability to act as protective esophageal irrigations until endoscopic removal of the BB.

Placental Mesenchymal Dysplasia without Fetal Development in a Twin Gestation: A Case Report and Review of the Spectrum of Androgenetic Biparental Mosaicism

We report a dichorionic twin gestation with diffuse placental mesenchymal dysplasia (PMD) and androgenetic biparental mosaicism (ABM) involving one twins placenta with complete absence of fetal development for that twin. To our knowledge, this is the 1st reported case of PMD without fetal development. We discuss the gross, histologic, and genetic hallmarks of PMD and the spectrum of variability depending on degree and distribution of ABM.

Correlation of probability scores of placenta accreta on magnetic resonance imaging with hemorrhagic morbidity

STUDY OBJECTIVE AND DESIGN To evaluate the hypothesis that assigning grades to magnetic resonance imaging (MRI) findings of suspected placenta accreta will correlate with hemorrhagic outcomes. We chose a single-center, retrospective, observational design. SETTING, PATIENTS, AND MEASUREMENTS Nulliparous or multiparous women who had antenatal placental MRI performed at a tertiary level academic hospital were included. Cases with antenatal placental MRI were included and compared with cases without MRI performed. Two radiologists assigned a probability score for accreta to each study. Estimated blood loss and transfusion requirements were compared among groups by the Kruskal-Wallis H test. RESULTS Thirty-five cases had placental MRI performed. MRI performance was associated with higher blood loss compared with the non-MRI group (2600 [1400-4500]mL vs 900[600-1500]mL, P<.001). There was no difference in estimated blood loss (P=.31) or transfusion (P=.57) among the MRI probability groups. CONCLUSIONS In cases of suspected placenta accreta, probability scores for antenatal placental MRI may not be associated with increasing degrees of hemorrhage. Continued research is warranted to determine the effectiveness of assigning probability scores for antenatal accreta imaging studies, combined with clinical indices of suspicion, in assisting with antenatal multidisciplinary team planning for operative management of this morbid condition.

In Response to pH-Neutralizing Esophageal Irrigations as a Novel Mitigation Strategy for Button Battery Injury : Letter to the Editor

We would like to thank Dr. Renny and colleagues for their comments related to our recent publication. Although it is difficult to use an animal model to recreate the exact scenario of a pediatric esophageal button battery (BB), randomized controlled human studies are not possible. We are up against a severe hazard, a caustic BB that rapidly generates hydroxide ions, and the clock begins ticking from the moment it becomes lodged in the esophagus. The progression of esophageal BB injuries can lead to debilitating injuries and death. Thus, the critical time period from ingestion to BB removal is a potential target for intervention(s) to improve patient outcomes. Prior to this work, no treatment options existed to help slow the rate of injury. It is our opinion that both the ability to neutralize pH, provide a physical barrier, and palatability are important. Lemon juice in prior studies was very effective with a low pH even though it was not as viscous as honey, but it would be unrealistic for most children to swallow it. In our in vitro and in vivo animal models, both honey and Carafate had protective effects compared to controls. Even though our overall sample size was limited, the improved outcomes were statistically significant compared to controls. To study these interventions in a highly standardized protocol and be able to look at the esophageal histopathology 7 days out, we had to use an animal model with interventions performed under anesthesia. We agree that it is not the exact scenario as an upright child, but point out that children with esophageal BB are often ill enough to not always be upright, and also point out that both the control and honey/Carafate interventions were given in a consistent manner to be able to compare them. It should be noted that esophageal perforations were only seen in the control animals. From an animal standpoint, there was enough data to show a clear difference of intervention compared to controls, and we did not feel it was justified to sacrifice additional animals. The risk and potential benefit of using a preremoval intervention like honey or Carafate when compared to the rapid injury caused by an esophageal BB has to be considered. The National Capital Poison Center Button Battery Triage and Treatment Guidelines have been updated to reflect our recently published data on the protective effects of honey and Carafate prior to removal. Those guidelines clearly state that these interventions are not a substitute for prompt BB removal. The intent is to slow injury and help to reduce potential morbidity, until removal can take place. In rural and some community hospital settings, a child may need to be transferred to a pediatric facility, further delaying removal. We certainly do not recommend having parents go buy honey, nor do we advise clinicians to delay getting a patient to the operating room to wait for honey or Carafate to be obtained and given. Because the guidelines changed in late June 2018 at Nationwide Childrens Hospital, both honey and Carafate are stocked and immediately available in the emergency room. These interventions are recommended in children over 12 months of age who can swallow, and the suspected or witnessed ingestion occurred within 12 hours. The 12-hour time frame is based on available human data, where there is extremely low likelihood of an existing perforation or early stage mediastinitis where oral intake should be avoided. In addition, this is the interval where such intervention may provide the maximal benefit to prevent esophageal perforation. When swallowed, honey or Carafate goes from the proximal to distal in the esophagus and the exact coating around the BB in each child may be variable with intermittent swallowing of saliva, but using repeated small doses—about 10 mL (2 teaspoons) every 10 minutes—will allow for greater likelihood of maintaining a protective coating. In the guidelines, honey given in up to 6 doses prehospital, and then either honey or Carafate given in up to 3 additional doses in the emergency room (after x-ray confirmation) serve as a benchmark, keeping in mind the general anesthesia needed for removal. However, it is important to recognize that most children who are discovered to have an esophageal BB are going to the operating room emergently are not NPO. Nationally recognized pediatric anesthesia specialists have reviewed our data, as well as the latest guidelines; they determined anesthetic-related risks like aspiration are low with rapid sequence induction techniques, *Co-Principal Investigators

Ovotestis in Adolescence: 2 Case Reports

We present 2 patients found to have ovotesticular disorder of sexual development (otDSD) in late adolescence. Two 15-year-old phenotypically male patients presented to a large pediatric hospital with different complaints: 1 with concern for testicular rupture after a straddle injury; 1 with gynecomastia. Further workup, including imaging and laboratory tests, was performed before surgical exploration. The first patient had unilateral ovotestis, contralateral testis, and SRY-negative 46,XX karyotype. The second patient with gynecomastia had unilateral ovotestis with hemi-uterus and fallopian tube, contralateral ovarian tissue, and 46,XX/47,XXY Klinefelter mosaic karyotype. Although rare, phenotypically normal male patients may present later with ovotesticular disorder of sexual development.