Triaging and Evaluation of Products of Conception in Abortions and Post-Partum Hemorrhage.

The proper evaluation of abortion specimens and placentas from stillbirth and post-partum cases is important for adequate clinical care of post-abortion and post-partum patients. The following topics will be reviewed: (1) the importance of evaluation of both fetal and placental tissue in first trimester abortions to confirm an intrauterine pregnancy versus an ectopic pregnancy; (2) the clinical history associated with an abortion specimen or retained products of conception (POC) influences how the pathologist should triage the specimen; (3) the criteria for diagnosis of a molar pregnancy, which is critical for clinicians to know which patients need follow-up; (4) the utility of genetic studies for both diagnosis and appropriate follow-up of the patient; and (5) the pathologic evaluation of specimens from patients with post-partum hemorrhage for placenta accreta spectrum and subinvolution of maternal vessels.

Bulk RNA sequencing of human pediatric lung cell populations reveals unique transcriptomic signature associated with postnatal pulmonary development.

Postnatal lung development results in an increasingly functional organ prepared for gas exchange and pathogenic challenges. It is achieved through cellular differentiation and migration. Changes in the tissue architecture during this development process are well-documented and increasing cellular diversity associated with it are reported in recent years. Despite recent progress, transcriptomic and molecular pathways associated with human postnatal lung development are yet to be fully understood. In this study, we investigated gene expression patterns associated with healthy pediatric lung development in four major enriched cell populations (epithelial, endothelial, and nonendothelial mesenchymal cells, along with lung leukocytes) from 1-day-old to 8-yr-old organ donors with no known lung disease. For analysis, we considered the donors in four age groups [less than 30 days old neonates, 30 days to < 1 yr old infants, toddlers (1 to < 2 yr), and children 2 yr and older] and assessed differentially expressed genes (DEG). We found increasing age-associated transcriptional changes in all four major cell types in pediatric lung. Transition from neonate to infant stage showed highest number of DEG compared with the number of DEG found during infant to toddler- or toddler to older children-transitions. Profiles of differential gene expression and further pathway enrichment analyses indicate functional epithelial cell maturation and increased capability of antigen presentation and chemokine-mediated communication. Our study provides a comprehensive reference of gene expression patterns during healthy pediatric lung development that will be useful in identifying and understanding aberrant gene expression patterns associated with early life respiratory diseases.NEW & NOTEWORTHY This study presents postnatal transcriptomic changes in major cell populations in human lung, namely endothelial, epithelial, mesenchymal cells, and leukocytes. Although human postnatal lung development continues through early adulthood, our results demonstrate that greatest transcriptional changes occur in first few months of life during neonate to infant transition. These early transcriptional changes in lung parenchyma are particularly notable for functional maturation and activation of alveolar type II cell genes.

Placental ferroportin protein abundance is associated with neonatal erythropoietic activity and iron status in newborns at high risk for iron deficiency and anemia.

BACKGROUND: Murine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting. OBJECTIVES: This study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia. METHODS: Placental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 ± 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 ± 1.3 wk) and from 130 neonates born to 65 females (30.4 ± 5.2 y) carrying multiples (delivery GA: 35.0 ± 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone). RESULTS: FPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: ß: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: ß: 0.20; 95% CI: 0.03, 0.18; hepcidin: ß: -0.06; 95% CI: -0.13, -0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (ß-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (ß: -0.02; 95% CI: -0.03, -0.003), EPO (ß: 0.07; 95% CI: 0.01, 0.14), and sTfR (ß: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (ß: 0.08, 95% CI: 0.02, 0.14), TBI (ß: 0.02; 95% CI: 0.009, 0.04), EPO (ß: -0.10; 95% CI: -0.19, -0.01), sTfR (ß: -0.16: 95% CI: -0.27, -0.06), and hepcidin (ß: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05). CONCLUSIONS: Placental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings. These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.

New insights into the natural history of bronchopulmonary dysplasia from proteomics and multiplexed immunohistochemistry.

Bronchopulmonary dysplasia (BPD) is a disease of prematurity related to the arrest of normal lung development. The objective of this study was to better understand how proteome modulation and cell-type shifts are noted in BPD pathology. Pediatric human donors aged 1-3 yr were classified based on history of prematurity and histopathology consistent with "healed" BPD (hBPD, n = 3) and "established" BPD (eBPD, n = 3) compared with respective full-term born (n = 6) age-matched term controls. Proteins were quantified by tandem mass spectroscopy with selected Western blot validations. Multiplexed immunofluorescence (MxIF) microscopy was performed on lung sections to enumerate cell types. Protein abundances and MxIF cell frequencies were compared among groups using ANOVA. Cell type and ontology enrichment were performed using an in-house tool and/or EnrichR. Proteomics detected 5,746 unique proteins, 186 upregulated and 534 downregulated, in eBPD versus control with fewer proteins differentially abundant in hBPD as compared with age-matched term controls. Cell-type enrichment suggested a loss of alveolar type I, alveolar type II, endothelial/capillary, and lymphatics, and an increase in smooth muscle and fibroblasts consistent with MxIF. Histochemistry and Western analysis also supported predictions of upregulated ferroptosis in eBPD versus control. Finally, several extracellular matrix components mapping to angiogenesis signaling pathways were altered in eBPD. Despite clear parsing by protein abundance, comparative MxIF analysis confirms phenotypic variability in BPD. This work provides the first demonstration of tandem mass spectrometry and multiplexed molecular analysis of human lung tissue for critical elucidation of BPD trajectory-defining factors into early childhood.NEW & NOTEWORTHY We provide new insights into the natural history of bronchopulmonary dysplasia in donor human lungs after the neonatal intensive care unit hospitalization. This study provides new insights into how the proteome and histopathology of BPD changes in early childhood, uncovering novel pathways for future study.

Placental Erythroferrone and Erythropoietin mRNA Expression is not Associated with Maternal or Neonatal Iron Status in Adolescents Carrying Singletons and Adult Women Carrying Multiples.

BACKGROUND: The iron regulatory hormones erythroferrone (ERFE), erythropoietin (EPO), and hepcidin, and the cargo receptor nuclear receptor coactivator 4 (NCOA4) are expressed in the placenta. However, determinants of placental expression of these proteins and their associations with maternal or neonatal iron status are unknown. OBJECTIVES: To characterize expression of placental ERFE, EPO, and NCOA4 mRNA in placentae from newborns at increased risk of iron deficiency and to evaluate these in relation to maternal and neonatal iron status and regulatory hormones. METHODS: Placentae were collected from 114 neonates born to adolescents carrying singletons (14-18 y) and 110 neonates born to 54 adults (20-46 y) carrying multiples. Placental EPO, ERFE, and NCOA4 mRNA expression were measured by RT-qPCR and compared with maternal and neonatal iron status indicators (SF, sTfR, total body iron, serum iron) and hormones. RESULTS: Placental ERFE, EPO, and NCOA4 mRNA were detected in all placentae delivered between 25 and 42 wk of gestation. Relationships between placental ERFE and EPO differed by cohort. In the multiples cohort, placental EPO and ERFE were positively correlated (P = 0.004), but only a positive trend (P = 0.08) was evident in the adolescents. Placental EPO and ERFE were not associated with maternal or neonatal iron status markers or hormones in either cohort. Placental NCOA4 was not associated with placental EPO or ERFE in either cohort but was negatively associated with maternal SF (P = 0.03) in the multiples cohort and positively associated with neonatal sTfR (P = 0.009) in the adolescents. CONCLUSIONS: The human placenta expresses ERFE, EPO, and NCOA4 mRNA as early as 25 wk of gestation. Placental expression of ERFE and EPO transcripts was not associated with maternal or neonatal iron status. Greater placental NCOA4 transcript expression was evident in women and newborns with poor iron status (lower SF and higher sTfR, respectively). Further research is needed to characterize the roles of these proteins in the human placenta. TRIAL REGISTRATION NUMBER: These clinical trials were registered at clinicaltrials.gov as NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902) and NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802).

Umbilical Appendix Masquerading as a Patent Omphalomesenteric Duct in a Neonate.

The umbilicus is the site of a number of well-recognized and unusual abnormalities. Well-known neonatal umbilical abnormalities include umbilical hernias, granulomas/polyps, and congenital remnants of development. In this article, we describe a rare case of an appendix draining through the umbilicus of a neonate. In the literature, there are only 15 cases with possible umbilical appendix. We describe this rare case along with a review of the literature and discuss the underlying pathophysiology.

Placental Iron Content Is Lower than Previously Estimated and Is Associated with Maternal Iron Status in Women at Greater Risk of Gestational Iron Deficiency and Anemia.

BACKGROUND: Based on limited data, it is estimated that the placenta retains 90 mg of iron. Little is known about determinants of placental iron content. Animal data indicate that the placenta prioritizes iron for its own needs, but this hypothesis has not been evaluated in humans. OBJECTIVES: To characterize placental iron content and placental iron concentration (p[Fe]) in pregnant women at risk of iron insufficiency and identify determinants of p[Fe]. METHODS: Placentas were collected from 132 neonates born to teens carrying singletons (≤18 y) and 101 neonates born to 48 women carrying multiples (20-46 y). Maternal and neonatal iron status indicators [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), serum iron, total body iron (TBI)] and hormones (erythropoietin, hepcidin) were measured. p[Fe] was measured using inductively coupled plasma-mass spectrometry. Correlation analyses and mixed-effects models were constructed to identify determinants of p[Fe]. RESULTS: Mean placental iron content was 23 mg per placenta (95% CI: 15, 33 mg) in the multiples and 40 mg (95% CI: 31, 51 mg) in the teens (P = 0.03). Mean p[Fe] did not differ between the cohorts. p[Fe] was higher in anemic (175 µg/g; 95% CI: 120, 254 µg/g) compared with nonanemic (46 µg/g; 95% CI: 26, 82 µg/g) women carrying multiples (P = 0.009), but did not differ between anemic (62 µg/g; 95% CI: 40, 102 µg/g) and nonanemic (73 µg/g; 95% CI: 56, 97 µg/g) teens. In women carrying multiples, low maternal iron status [lower SF (P = 0.002) and lower TBI (P = 0.01)] was associated with higher p[Fe], whereas in teens, improved iron status [lower sTfR (P = 0.03) and higher TBI (P = 0.03)] was associated with higher p[Fe]. CONCLUSIONS: Placental iron content was ∼50% lower than previously estimated. p[Fe] is significantly associated with maternal iron status. In women carrying multiples, poor maternal iron status was associated with higher p[Fe], whereas in teens, improved iron status was associated with higher p[Fe]. More data are needed to understand determinants of p[Fe] and the variable iron partitioning in teens compared with mature women.

A Young Boy With Hemophagocytic Lymphohistiocytosis Presenting With Vaccine-Related Granulomatous Dermatitis: A Case Report and Literature Review.

ABSTRACT: Cutaneous eruptions associated with hemophagocytic lymphohistiocytosis (HLH) have been reported in 6%-63% of patients. Clinical findings of these skin lesions vary widely and include maculopapular rashes, ulcers, and violaceous nodules. Corresponding histologic findings are also variable and are considered nonspecific. We report the case of a 4-year-old boy who initially developed a widespread popular-pustular rash 2 weeks after his 12-month measles, mumps, and rubella vaccinations. These resolved with scarring then recurred following his 24-month vaccinations. Multiple skin biopsies were negative for infectious organisms and showed a granulomatous infiltrate with perforation and necrobiosis. The differential diagnosis included perforating granuloma annulare, infection, or rheumatoid nodules. At the age of 4, he developed fever, hepatosplenomegaly, pancytopenia and other laboratory abnormalities, requiring hospitalization. A number of studies were performed including biopsies of bone marrow and liver. Molecular testing revealed 2 mutations in UNC13D known to be associated with familial HLH. His prior cutaneous lesions were likely caused by immune dysregulation exacerbated by immunizations because of underlying familial HLH. This case illustrates the importance of recognizing an unusual cutaneous manifestation of a rare disease to arrive at an earlier diagnosis in a pediatric patient. Although cutaneous eruptions usually develop concurrently with other systemic symptoms of HLH, preceding unusual skin lesions may be the first indication of this rare disease.

Myocardial Calcification and the Demise of an Infant With Surgically Treated Hypoplastic Left Heart Syndrome.

A term female infant with hypoplastic left heart syndrome underwent Norwood palliation including aortic and pulmonary amalgamation with arch reconstruction, atrial septectomy, and right ventricle to pulmonary artery conduit. Postoperatively, she experienced hypoxemia and lactic acidosis although echocardiogram showed adequate conduit function. She was placed on veno-arterial extracorporeal membrane oxygenation (ECMO) on postoperative day two with improvement. ECMO decannulation was attempted with subsequent cardiac arrest and ultimate failure to resuscitate, eleven days after surgery. Autopsy confirmed clinical findings and evidence of surgical intervention with a patent conduit and neo-aorta. Multiple subendocardial right ventricular dystrophic calcifications involving the outflow tract were identified grossly and histologically with foci of associated myonecrosis. Myocardial calcification may lead to abnormal heart wall motion by increasing rigidity and compromising myocyte function or compromising the conduction system. In this patient, right ventricular turbulence caused by systolic and diastolic flow patterns, including mild tricuspid regurgitation, may have played a role in inducing dystrophic calcification along with surgery and ECMO dependence. Compromised myocyte function from calcifications, right ventricular hypertrophy, lung immaturity, and persistent pulmonary hypertension were likely sources of cardiac strain leading to the patient's demise. This case represents a previously unreported complication of hypoplastic left heart syndrome treatment.

Classification and reporting guidelines for the pathology diagnosis of placenta accreta spectrum (PAS) disorders: recommendations from an expert panel.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Superior Vena Cava Syndrome and Hypoxic Ischemic Encephalopathy Secondary to a Massive, Right-Sided Immature Cervical Teratoma.

Cervical teratomas are a rare form of fetal teratoma that can grow to massive size. Generally, these masses can be surgically excised after birth with excellent physical and functional prognosis because the benign variants respect anatomical borders. The primary complications of these masses are associated with compromise of the trachea and esophagus: upper airway obstruction and polyhydramnios. We report the first documented occurrence of superior vena cava syndrome and hypoxic ischemic encephalopathy associated with a massive, right-sided cervical teratoma. This case highlights that when cervical teratomas are right-sided and sufficiently large, they can extend inferiorly and compromise central venous return to the heart. This unique presentation would likely have required fetal surgical excision to avoid catastrophic cerebral injury.

Placental Chorionic Cyst Fluid Has Prothrombotic Properties and Differs From Amniotic Fluid.

INTRODUCTION: Chorionic cysts of the chorion laeve, fetal chorionic plate, septum, and free membranes have been associated with placental hypoxia, but they have no clear clinical significance. Although immunohistochemistry has identified fibronectin and collagen IV in cyst fluid, the contents have yet to be fully characterized. METHODS: Placental chorionic cysts (N = 10) were sampled by fluid extraction and hemotoxylin and eosin-stained sections. Amniotic fluid samples (N = 8) were obtained from pregnant women who had cytogenetic evaluation. The content of the cysts was tested for thrombogenicity using thromboelastography. The cyst content was tested by Luminex multiplex and ELISA assays and for known prothrombotic and proinflammatory factors. RESULTS: We identified cysts, especially those in the chorionic plate, adjacent to intervillous thrombi with apparent cyst rupture. Thromboelastography revealed a significantly shorter R time compared to whole blood control samples. Concentration of creatinine, α-fetoprotein, and surfactant D in the cyst fluid differed significantly from amniotic fluid. Cyst fluids had a significantly higher expression of all prothrombotic and some proinflammatory factors. DISCUSSION: Our data provide the first evidence that chorionic cyst fluid is prothrombotic and different from amniotic fluid. The association of ruptured cysts with adjacent thrombi and the prothrombotic properties of cyst fluid suggest a causal relationship; however, further studies are needed.

Unexpectedly High Prevalence of Cystoisospora belli Infection in Acalculous Gallbladders of Immunocompetent Patients.

Objectives: Indications for cholecystectomy have changed dramatically over the past three decades. Cystoisospora belli has been reported in cholecystectomy specimens of immunocompetent patients. The present study was designed to determine the prevalence and clinical association of C belli in the gallbladder. Methods: The study included retrospective review of cholecystectomy specimens (n = 401) removed for various indications, and a prospective cohort of cholecystectomy specimens (n = 22) entirely submitted for histologic evaluation. Correlations of presence of C belli with age, sex, clinical indication, and abnormalities of preoperative laboratory values were assessed by Fisher exact test. Results: C belli was identified in 39/401 (9.7%) of the retrospective cohort, and 6/22 (27.3%) of the entirely submitted specimens. The presence of C belli showed no correlation with age, sex, clinical indication, or laboratory abnormalities. Conclusions: C belli resides in a latent state in the gallbladder and may be best considered a commensal organism.

Umbilical Cord Hepcidin Concentrations Are Positively Associated with the Variance in Iron Status among Multiple Birth Neonates.

Background: Hepcidin is a systemic regulator of iron homeostasis. Little is known about the relative role of maternal compared with cord hepcidin on neonatal iron homeostasis. Objective: This study was undertaken to evaluate inter- and intrauterine variance in neonatal iron status, vitamin B-12, folate, and inflammatory markers in a cohort of twins (n = 50), triplets (n = 14), and quadruplets (n = 1) born to 65 women. Methods: Umbilical cord blood was obtained from 144 neonates born at 34.8 ± 2.7 wk of gestation with a mean birth weight of 2236 ± 551 g (means ± SDs). Cord hemoglobin and cord serum measures of ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, erythropoietin (EPO), iron, vitamin B-12, folate, interleukin 6, and C-reactive protein were evaluated. Results: Intraclass correlation coefficient (ICC) analyses were used to examine inter- and intrauterine variance in neonatal iron indicators. A greater variability in cord hepcidin (ICC = 0.39) was found between siblings. Cord hepcidin had the greatest association with cord iron indicators because cord hepcidin alone captured 63.8%, 48.4%, 44.4%, and 31.3% of the intrauterine variance in cord hemoglobin, SF, sTfR, and EPO, respectively, whereas maternal hepcidin had no effect on cord iron indicators. Significantly greater differences in cord SF (P = 0.03), sTfR (P = 0.03), hepcidin (P = 0.0003), and EPO (P = 0.03) were found between di- and trichorionic siblings than between monochorionic siblings. In contrast, cord folate (ICC = 0.79) and vitamin B-12 (ICC = 0.74) exhibited a greater variability between unrelated neonates. Conclusions: In summary, fetally derived hepcidin might have more control on intrauterine variance in iron indicators than maternal hepcidin and appears to be capable of regulating fetal iron status independently of maternal hepcidin. The use of a multiple-birth model provides a unique way to identify factors that may contribute to placental nutrient transport and iron stores at birth.

Neonatal neuroblastoma 4s with diffuse liver metastases (Pepper syndrome) without an adrenal/extraadrenal primary identified on imaging.

We report the imaging appearances of a case of pathologically proven, neonatal neuroblastoma 4S with diffuse hepatic metastatic involvement at presentation. Patient had an abnormal appearing liver both by ultrasound and MR. There was no evidence for associated adrenal tumor by imaging. Lack of an associated adrenal mass led to initial misinterpretation of diffuse hepatic accumulation of MIBG seen with radionuclide scintigraphy. To the best our knowledge, this is the first report of metastatic neonatal 4S neuroblastoma without an adrenal (or extra-adrenal) primary identified either on pre- or post-natal imaging.

Predictors of anemia and iron status at birth in neonates born to women carrying multiple fetuses.

BACKGROUND: Iron (Fe) status of neonates born to women carrying multiple fetuses might be compromised as a consequence of the high prevalence of maternal Fe deficiency and anemia coupled with an increased risk of preterm birth. This study aimed to characterize and identify determinants of anemia in this neonatal population. METHODS: Umbilical cord blood obtained from 183 neonates was utilized to assess hemoglobin (Hb), ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum Fe, erythropoietin, folate, vitamin B-12, C-reactive protein, and interleukin-6. Associations with maternal Fe status were explored. RESULTS: Cord Hb or SF did not change significantly as a function of gestational age at birth (25-38 wks). Neonates born to women who were obese prior to pregnancy or smoked cigarettes during pregnancy had a 4-5-fold greater odds of anemia at birth. Cord sTfR was the strongest indicator of cord Hb (P < 0.0001), and it was significantly associated with maternal sTfR at mid-gestation (P = 0.01) and delivery (P = 0.002). Cord Fe indicators were significantly associated with cord hepcidin, but not maternal hepcidin. CONCLUSION: Screening for Fe status in neonates born to women carrying multiple fetuses is warranted, especially for those born to smokers or to women who are obese at entry into pregnancy.

Umbilical Cord Coiling in High-risk Pregnancies: Associations With Determinants of Adverse Birth Outcomes and Iron Status.

Abnormal umbilical cord coiling has been associated with adverse neonatal outcomes, but the etiology of these findings remains poorly characterized. This study was undertaken to examine associations between cord coiling and maternal iron (Fe) status and to identify potential determinants of hypo- and hypercoiling in 2 higher risk obstetric groups: pregnant adolescents (≤18 years, n = 92) and adult women carrying twins (n = 49), triplets (n = 11), or quadruplets (n = 1). Umbilical cords were classified as hypo-, normo-, or hypercoiled using digital photographs to assess gross appearance. Hypocoiling and hypercoiling were observed in 44% (n = 86/195) and 13% (n = 26/195) of the combined study population. The prevalence of hypocoiling among women carrying multiples was over 3-fold higher than the prevalence in singleton pregnancies based on the published data. Within the entire study population, hypocoiling was associated with a lower gestational age at birth when compared to normocoiling and hypercoiling (36.3 ± 3.6 weeks [n = 86] vs 37.8 ± 2.7 [n = 83], P < .01, and 38.2 ± 2.6 [n = 26], P < .01, respectively), whereas hypercoiling was associated with significantly lower serum ferritin when compared to normocoiling ( P < .01) and hypocoiling ( P < .001). In the multiples cohort only, hypercoiling was significantly associated with multiparity ( P < .01) and lower birth weight ( P < .05). Further studies are needed to identify the determinants and consequences of cord coiling.

Congenital Diaphragmatic Hernia with Liver Herniation into the Pericardial Sac in a 30-Week Gestation Infant.

Anterior diaphragmatic defects with pericardial involvement are extremely rare and diagnostically challenging entities encountered perinatally. While a majority of diaphragmatic defects occur in isolation, others are associated with multiple defects forming a complex of syndromes such as Pentalogy of Cantrell. Liver herniation into the pericardial sac poses a particular challenge and can mimic a pericardial tumor on prenatal ultrasound, yielding a different management course. The following case is an unusual presentation of a 30-week gestation female with an anterior midline diaphragmatic defect with liver herniation mimicking as a pericardial tumor, diagnosed at time of autopsy. Postmortem studies also found multiple congenital anomalies including an atrioventricular septal defect and midline gumline defect suggesting at least a partial Pentalogy of Cantrell or variant. Early recognition and screening for associated anomalies are essential for management in this subset of patients.