Placental histology for targeted risk assessment of recurrent spontaneous preterm birth.

BACKGROUND: Spontaneous preterm birth significantly increases the risk for a recurrent preterm birth. Only a few identifiable clinical risk factors can be referenced in counseling for recurrent preterm birth. Furthermore, treatment using progesterone supplementation has not consistently prevented preterm birth among high-risk patients, but it may be effective in a subset of those patients. Placental pathology from a previous pregnancy may be used to predict which patients will experience a recurrent preterm birth or to identify a subset of patients more likely to respond to treatment with antenatal progesterone. OBJECTIVE: This study aimed to determine if histologic patterns are associated with recurrent preterm birth among patients with an index spontaneous preterm birth. A secondary objective was to determine if placental histologic types and/or progesterone receptor density in the decidua are associated with the response to progesterone supplementation with intramuscular 17-hydroxyprogesterone caproate. STUDY DESIGN: This was a retrospective cohort study at a single institution of women with singleton pregnancies with an index spontaneous preterm birth and a subsequent birth within the same hospital system between 2009 and 2019. Patients were included if placental pathology was available for the index spontaneous preterm birth. A logistic regression was used to determine if there were independent associations between 4 histologic types (acute inflammation, maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammation) and recurrent preterm birth. For the secondary endpoint, 17-hydroxyprogesterone caproate response was defined as prolonging gestation by >3 weeks beyond the gestational age at delivery in the index pregnancy. Patients who delivered <3 weeks beyond the gestational age in the index pregnancy but at ≥39 weeks' gestation were excluded. A logistic regression was used to assess the independent association between placental histology and 17-hydroxyprogesterone caproate response. Sensitivity analyses were completed using only patients with an index birth <36 weeks' gestation, and then excluding those with medically indicated preterm birth in a subsequent pregnancy. A nested case-control immunohistochemical study was done among 20 patients with a subsequent term birth and 20 patients with a subsequent spontaneous preterm birth. The percentage of cells in the maternal decidua positive for progesterone receptors was correlated with the subsequent pregnancy outcome. RESULTS: A total of 352 patients were included. Acute inflammation was the most common histologic type seen among patients with spontaneous preterm birth (44.1%), followed by chronic inflammation (40.9%) and maternal vascular malperfusion (31.3%). No histologic type was independently associated with recurrent preterm birth. A total of 155 patients received 17-hydroxyprogesterone caproate in a second pregnancy. Low-grade acute inflammation was significantly associated with a decreased likelihood of 17-hydroxyprogesterone caproate response. Low-grade maternal vascular malperfusion among those with an index pregnancy delivered at <36 weeks' gestation was significantly associated with a more than 4 times increased likelihood of 17-hydroxyprogesterone caproate response when excluding those with a subsequent iatrogenic preterm birth. Progesterone receptor staining was not associated with recurrent preterm birth. CONCLUSION: Although acute inflammation was prevalent among spontaneous preterm births, more than half of the spontaneous preterm births were not associated with acute inflammation. Low-grade acute inflammation was associated with a significantly decreased response to 17-hydroxyprogesterone caproate supplementation. Low-grade maternal vascular malperfusion was associated with a 4-fold increased likelihood of 17-hydroxyprogesterone caproate response among those with index deliveries <36 weeks' gestation. Further work is needed to determine if placental pathologic examination can be used to target treatment in subsequent pregnancies to prevent recurrent preterm birth.

Stillbirth Associated With Anomalous Origin and Course of the Left Coronary Artery: A Report of 2 Cases.

Coronary artery anomalies and their potential sequelae are not well studied in association with stillbirth. Herein, we report the autopsy findings in two term stillborn fetuses with coronary artery anomalies. Both fetuses showed identical findings consisting of an abnormal origin of the left coronary artery from the right sinus of Valsalva and an interarterial course of the left coronary artery. Histologic vascular and myocardial changes were also present. These coronary artery findings are associated with sudden death in adults and neonates, and therefore, their potential to be a cause and/or contributor to fetal death is suspected.

Decreased Alpha Klotho Expression in Placentas Exposed to Severe Maternal Vascular Malperfusion.

BACKGROUND: Placental maternal vascular malperfusion (MVM) is characterized by accelerated villous maturation and has been associated with a decrease in the antiaging protein, alpha-klotho (AK). Our aim was to characterize AK protein and gene expression in the placenta and fetal organs. METHODS: We utilized 2 cohorts. First, we characterized AK protein expression in an autopsy cohort where cases were defined as MVM as the cause of fetal death compared to a stillborn control population. Second, we characterized placental and umbilical cord blood AK gene expression in a liveborn population with and without MVM. RESULTS: We found decreased protein expression in the villous trophoblastic cells of placentas exposed to severe MVM and decreased AK gene expression in placental tissue exposed to MVM. We did not see any statistically significant differences in fetal organ or umbilical cord blood AK expression based on the presence or absence of MVM. Furthermore, in liveborn infants, we also found increased odds of preterm birth with lower placental AK expression. CONCLUSIONS: Decreased AK gene and protein expression in the placenta in the setting of MVM is consistent with the theory of placental aging in MVM and is associated with increased odds of preterm birth.

Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease.

The importance of a fully functioning placenta for a good pregnancy outcome is unquestioned. Loss of function can lead to pregnancy complications and is often detected by a thorough placental pathologic examination. Placental pathology has advanced the science and practice of obstetrics and neonatal-perinatal medicine by classifying diseases according to underlying biology and specific patterns of injury. Many past obstacles have limited the incorporation of placental findings into both clinical studies and day-to-day practice. Limitations have included variability in the nomenclature used to describe placental lesions, a shortage of perinatal pathologists fully competent to analyze placental specimens, and a troubling lack of understanding of placental diagnoses by clinicians. However, the potential use of placental pathology for phenotypic classification, improved understanding of the biology of adverse pregnancy outcomes, the development of treatment and prevention, and patient counseling has never been greater. This review, written partly in response to a recent critique published in a major obstetrics-gynecology journal, reexamines the role of placental pathology by reviewing current concepts of biology; explaining the most recent terminology; emphasizing the usefulness of specific diagnoses for obstetrician-gynecologists, neonatologists, and patients; previewing upcoming changes in recommendations for placental submission; and suggesting future improvements. These improvements should include further consideration of overall healthcare costs, cost-effectiveness, the clinical value added of placental assessment, improvements in placental pathology education and practice, and leveraging of placental pathology to identify new biomarkers of disease and evaluate novel therapies tailored to specific clinicopathologic phenotypes of both women and infants.

Criteria for placental examination for obstetrical and neonatal providers.

Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach. These criteria include indications in which placental pathology has clinical relevance, such as pregnancy loss, maternal infection, suspected abruption, fetal growth restriction, preterm birth, nonreassuring fetal heart testing requiring urgent delivery, preeclampsia with severe features, or neonates with early evidence of multiorgan system failure including neurologic compromise. We encourage a focused gross examination by the provider or an attendant at delivery for all placentas and provide guidance for this examination. We recommend that any placenta that is abnormal on gross examination undergo a complete pathology examination. In addition, we suggest practice criteria for placental pathology services, including a list of critical values to be used by the relevant provider. We hope that these sets of triage indications, criteria, and practice suggestions will facilitate appropriate submission of placentas for pathologic examination and improve its relevance to clinical care.

Comparison of the Autopsy and Placental Findings in Second vs Third Trimester Stillbirth.

BACKGROUND: The pathology of second trimester fetal loss is not well-characterized due to lack of comprehensive autopsy studies. The purpose of this study is to compare autopsy pathology of second trimester and third trimester stillbirth. METHODS: In this retrospective cohort study, fetal autopsies performed in-house with complete placental examination were included. From autopsy reports, maternal demographics, gestational age, sex, body and placental weight, congenital anomalies, and cause of death (COD) were obtained. Immediate COD was coded "probable" or "possible" according to Initial Causes of Fetal Death (INCODE). RESULTS: Among 68 second trimester and 54 third trimester fetal autopsies, at least 1 probable COD was identified in 59/68 (87%) second trimester and 44/54 (81%) third trimester cases. 42/68 (62%) second trimester and 28/54 (52%) third trimester fetuses had probable COD secondary to placental pathology. Among placental causes, 29/42 (69%) second trimester and 14/28 (50%) third trimester stillbirths were related to compromised fetal microcirculation with umbilical cord abnormality. CONCLUSIONS: Among stillborn first and second trimester fetuses who undergo autopsy, the most prevalent COD is pathologic placental conditions, particularly those associated with umbilical cord obstruction. This study stresses the importance of placenta examination for establishing COD in both second and third trimester fetuses.

Histopathologic Findings in Large for Gestational Age Placentas and Correlation With CD15 Immunohistochemistry.

BACKGROUND: The histopathology and CD15 expression in large for gestational age (LGA) placentas is not well-documented. METHODS: To analyze this, we utilized 2 separate cohorts of placentas from singleton term deliveries. LGA and appropriate for gestational age (AGA) placentas were compared for major histopathologies including acute and chronic inflammation, maternal and fetal vascular malperfusion, delayed villous maturation (DVM), and villous hypervascularity/chorangiosis. We also examined CD15 immunohistochemistry in LGA and AGA placentas. Stained slides were reviewed blinded to the placental weight. Five random 20× fields were scored semi-quantitatively for CD15 staining of villous capillaries on a scale of 0 to 5 (0 = 0%, 1 = 1%-5%, 2 = 5%-25%, 3 = 25%-50%, 4 = 50%-75%, and 5 = >75%). RESULTS: In 1 cohort, 1238 LGA and 7908 AGA placentas were identified. Patients with LGA placentas were significantly more likely to have higher birthweight babies, obesity, hypertensive disorders, pre-gestational, and gestational diabetes. Also, LGA placentas had a higher prevalence of fetal vascular malperfusion, DVM, and villous chorangiosis. In other cohort of 75 LGA placentas and 73 AGA controls, the average score of CD15 staining in villous capillaries was significantly higher amongst LGA placentas. CONCLUSION: We conclude that LGA placentas have increased expression of CD15 in villous capillary endothelium and higher prevalence of FVM, DVM, and villous chorangiosis than AGA placentas.

Anatomy of the Ductus Arteriosus in Fetal Autopsies: Correlations With Placental Pathology and Cause of Death.

BACKGROUND: Differences in the shape of the ductus arteriosus (DA), an important vascular shunt between the pulmonary artery and aorta, may reflect fetoplacental blood flow. Our aim was to examine tapering of the DA in a fetal autopsy population and correlate it with placental pathology and cause of death (COD). METHODS: This autopsy case control study of stillborn fetuses selected cases (tapered DA) and consecutive age-matched controls (no DA tapering) between January 2017 and January 2022. We abstracted demographic and clinical data from pathology reports. Autopsy data included COD and histologic evidence of fetal hypoxia. Placental pathology included umbilical cord abnormalities, acute and chronic inflammation, fetal vascular malperfusion (FVM), and maternal vascular malperfusion (MVM). RESULTS: We identified 50 cases and 50 controls. Gestational age ranged from 18 to 38 weeks. Maternal and fetal demographic characteristics did not differ significantly between cases and controls. COD related to an umbilical cord accident/FVM was significantly more prevalent in cases vs controls (46% vs 26%, P = .037), and FVM in the placenta, regardless of COD, trended higher in cases than controls. CONCLUSION: Tapering of the DA is present in stillborn fetuses and associated with COD related to fetal vascular blood flow obstruction.

Fetal Supraventricular Tachycardia: Histologic Evidence of Accessory Pathways Due to Incomplete Annulus Fibrosus Formation.

BACKGROUND: Atrioventricular (AV) reentrant tachycardia is a common type of supraventricular tachycardia (SVT) that occurs in the fetus and neonate. Although many tachycardias resolve within several weeks of birth or respond to medical management, disruptions in the cardiac annulus fibrosus and development of additional accessory pathways may lead to refractory dysrhythmia resulting in fetal hydrops and ultimately, fetal death. OBJECTIVES: While accessory pathways have been well documented anatomically in adult and childhood tachyarrhythmias, there are no reports of the histology of these pathways in human fetuses with SVT. RESEARCH DESIGN, SUBJECTS, MEASURES: This is a small case series of 2 fetuses with a history of SVT that resulted in fetal hydrops. RESULTS: In both cases, examination of the cardiac conduction system was unremarkable and examination of the atrioventricular junction revealed a focally thinned and/or discontinuous annulus fibrosus with documented direct continuity between the atrial and ventricular myocardium in 1 case. CONCLUSIONS: This case series demonstrates that thinning or absence of the annulus fibrosus is a feature seen in fetal SVT, and the development of subsequent aberrant AV connections due to defective formation of the annulus fibrosus suggests a possible cause for these arrhythmias.

Measures of Fetal Growth and Cardiac Structure in Stillbirths With Placental Maternal Vascular Malperfusion: Evidence for Heart Weight Sparing and Structural Cardiac Alterations in Humans.

BACKGROUND: Placental maternal vascular malperfusion (MVM) is associated with fetal growth restriction (FGR). While FGR increases the risk of cardiovascular disease, the impact of MVM on fetal cardiac structure is understudied. METHODS: We utilized a cohort of autopsied stillbirths; 29 with MVM as the cause of death and 21 with a cause of death unrelated to MVM. Fetal and organ weights and heart measurements were standardized by gestational age and compared between MVM and non-MVM stillbirths. Differences in standardized fetal organ and cardiac measures as compared to standardized fetal body weight were calculated to account for body size. RESULTS: MVM stillbirths had smaller organ and heart weights than non-MVM stillbirths; however, after accounting for gestational age, heart weight was the least affected among all organs. In an analysis of organ weights relative to body size, heart weights were 0.31 standard deviations (SD) larger than expected relative to body weight (95% CI: 0.04, 0.57). Right and left ventricle thicknesses and mitral valve circumference were also larger than expected relative to body weight. CONCLUSION: Stillbirth due to MVM was associated with relative sparing of heart weight and other heart measurements. The significance of these findings in liveborn infants needs further study.

A comprehensive analysis of the association between placental pathology and recurrent preterm birth.

BACKGROUND: Histologic examination of the placenta is often performed after preterm birth. Although placental examination cannot change the index pregnancy outcome, it may inform the risk of adverse outcomes in a subsequent pregnancy. Previous research has examined the association between individual histologic lesions and pregnancy outcomes without consistent results. OBJECTIVE: This study aimed to determine the independent contributions of the major placental pathology histologic types to recurrent preterm birth. STUDY DESIGN: This was a retrospective cohort study of deliveries at a tertiary care center from January 2009 to March 2018. Individuals with ≥2 births, an index birth of <37 weeks of gestation, and a placental pathology report from the index pregnancy were included. The presence of maternal vascular malperfusion, fetal vascular malperfusion, acute inflammation, and chronic inflammation was extracted from the pathology reports for each index placenta and classified as none, low grade, or high grade. A log-binomial model incorporating all 4 placental pathology histologic types, index gestational age, race, and maternal age was used to estimate the associations between each placental histologic type and risk of recurrent preterm birth. Moreover, 2-way interaction terms were studied among placental histologic types. In addition, 2 stratified analyses were completed on the basis of characteristics of the index preterm birth: (1) by late preterm (gestational age of 34-36 weeks) vs early-to-moderate preterm birth (<34 weeks) and (2) a subgroup analysis of those with spontaneous preterm birth. RESULTS: A total of 924 pregnancy pairs met the inclusion criteria. Only high-grade chronic inflammation was independently associated with an increased risk of recurrent preterm birth (adjusted risk ratio, 1.37; 95% confidence interval, 1.03-1.81). Stratified analysis by gestational age group demonstrated maternal vascular malperfusion was associated with recurrent preterm birth only among those with early preterm birth (adjusted risk ratio, 1.40; 95% confidence interval, 1.01-1.93). Among participants with spontaneous preterm labor, no association was found between pathology histologic types and risk of preterm birth. CONCLUSION: Among index preterm pregnancies, high-grade chronic placental inflammation was associated with recurrent preterm birth. Low-grade maternal vascular malperfusion was associated with recurrent preterm birth only among those with an early or moderate index preterm birth (<34 weeks of gestation). These findings may be useful in determining the risk profile for individual patients and may generate hypotheses as to the pathogenesis of recurrent preterm birth.

Formulating a Meaningful and Comprehensive Placental Phenotypic Classification.

INTRODUCTION: While many placental lesions have been identified and defined, the significance of multiple overlapping lesions has not been addressed. The purpose of our analysis was to evaluate overlapping patterns of placental pathology and determine meaningful phenotypes associated with adverse birth outcomes. METHODS: Placental pathology reports were obtained from a single hospital between 2009 and 2018. Placental lesions were grouped into four major categories: acute inflammation (AI), chronic inflammation (CI), maternal vascular malperfusion (MVM), and fetal vascular malperfusion (FVM). Within each category, lesions were classified as not present, low grade or high grade. Combinations of pathologies were evaluated in relation to preterm birth (<37 weeks) and small for gestational age (SGA) infant (birthweight <10th percentile). RESULTS: During the study period, 19,027 placentas were reviewed by pathologists. Results from interaction models indicate that MVM and MVM in combination with CI and/or FVM are associated with the greatest odds of SGA infant and PTB. When incorporating grade, we identified 21 phenotype groups, each with characteristic associations with the SGA infant and patterns of PTB. DISCUSSION: We have developed a comprehensive and meaningful placental phenotype that incorporates severity and multiplicity of placental lesions. We have also developed a web application to facilitate phenotype determination (https://placentaexpression.shinyapps.io/phenotype).

Adverse Pregnancy Outcomes Following the Assassination of John F. Kennedy in 1963.

INTRODUCTION: Women exposed to stressful events during pregnancy are thought to be at increased risk of adverse birth outcomes. However, studies investigating stressful events are often unable to control for important confounders, such as behavioral and genetic characteristics, or to isolate the impact of the stressor from other secondary effects. We used a discordant-sibling design, which provides stronger inferences about causality, to examine whether a widespread stressor with limited impact on day-to-day life (John F. Kennedy assassination) resulted in an increased risk of adverse birth outcomes. METHODS: Data were obtained from the Collaborative Perinatal Project, a prospective, multi-site cohort study conducted in the US from 1959 to 1965. Our analysis was restricted to singleton live births ≥24 weeks born before the assassination (n = 24,406) or in utero at the time (n = 5833). We also evaluated associations within siblings discordant for exposure (n = 1144). We used survival analysis to evaluate associations between exposure and preterm birth and marginal models to evaluate associations with birthweight and placental pathology. RESULTS: First trimester exposure was associated with preterm birth (hazard ratio (HR): 1.17; 95% CI: 1.05, 1.31). In the discordant-sibling model, the point estimate was similar (HR: 1.22; 95% CI: 0.36, 4.06). Third trimester exposure was associated with increased odds of fetal acute inflammation in the placenta (odds ratio (OR): 1.34, 95% CI: 1.05, 1.71). CONCLUSIONS FOR PRACTICE: First trimester exposure to an acute stressor was associated with preterm birth. We did not observe increased odds of placental pathology with first trimester exposure; however, stress may increase preterm birth risk through chronic placental inflammation, which was not evaluated in this sample.

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.

Perinatal Pulmonary Hemorrhage: A Retrospective Autopsy Case Series.

Perinatal pulmonary hemorrhage (PH) is a condition characterized by blood loss via the respiratory tract with an approximate incidence of 0.1% in all newborns. The histologic characteristics of the lung in PH are not well characterized, and we hypothesized that pulmonary maldevelopment such as pulmonary hypoplasia may contribute to PH. In addition, we sought to find any correlations with placental pathology. Retrospective study of fetal and neonatal autopsies with diagnosis of PH was performed between the years from 2009 to 2015. Autopsy reports, placental pathology reports, and hematoxylin and eosin sections of the lung were reviewed. Of the 17 cases which were identified meeting inclusion criteria, PH ranged from mild (<5% in each lung) to severe (>75% in both lungs). PH involved >50% of both lungs in 6 cases. Pulmonary hypoplasia was designated in 7 of 17 (41.17%) cases with PH. Pulmonary hypoplasia and/or persistence of intra-acinar arterioles was seen in 13 of 17 (76.4%) cases. No specific placental pathology was seen universally in the cases of PH, but either maternal or fetal vascular malperfusion was noted in 14 of 17 (82%) cases. Our data suggest a high prevalence of pulmonary maldevelopment, such as pulmonary hypoplasia and persistence of intra-acinar arterioles, in cases with PH. Although no specific placental pathology is seen in PH, maternal and fetal vascular pathology is common.

Cartilaginous Metaplasia Involving the Atrioventricular Node and Bundle of His Contributing to Sudden Early Neonatal Death.

Cartilaginous metaplasia involving the atrioventricular (AV) node is an uncommon entity that may cause sudden cardiac death secondary to dysrhythmias. We report 2 autopsy cases of full-term male newborns: 1 stillborn and 1 live-born, with antemortem bradycardia who died in the peripartum period. An examination of the cardiac conduction system in both cases demonstrated extensive cartilaginous metaplasia of the central fibrous body and involvement of the AV node and bundle of His. The cases highlight the recognition of cardiac conduction system anomalies as a cause of sudden perinatal death. In cases of perinatal death with preceding arrhythmia, postmortem sections of the cardiac conduction system are recommended to examine for cardiac conduction system anomaly.

Correlation of Placental Magnetic Resonance Imaging With Histopathologic Diagnosis: Detection of Aberrations in Structure and Water Diffusivity.

OBJECTIVE: Noninvasive methods to identify placental pathologic conditions are being sought in order to recognize these conditions at an earlier stage leading to improved clinical interventions and perinatal outcomes. The objective of this study was to examine fixed tissue slices of placenta by T2- and diffusion-weighted magnetic resonance imaging (MRI) and correlate the images with placental pathologic findings defined by routine gross and histologic examination. METHODS: Four formalin-fixed placentas with significant placental pathology (maternal vascular malperfusion, chronic villitis of unknown etiology, and massive perivillous fibrin deposition) and 2 histologically normal placentas were evaluated by high-resolution MRI. Representative placental slices were selected (2 cm long and 10 mm wide) and rehydrated. Imaging was performed on a Bruker Avance 14.1 T microimager. Diffusion-weighted images were acquired from 16 slices using slice thickness 0.5 mm and in-plane resolution approximately 100 µm × 100 µm. T2 maps were obtained from the same slices. T2 relaxation time and apparent diffusion coefficient (ADC) were acquired from representative regions of interest and compared between normal and diseased placentas. RESULTS: In T2- and diffusion-weighted images, the placental microstructure differed subjectively between diseased and normal placentas. Furthermore, diseased placentas showed statistically significantly longer mean T2 relaxation times and generally higher mean ADC. CONCLUSION: Diffusion- and T2-weighted MRI can potentially be used to detect significant placental pathology by using T2 relaxation time and ADC as markers of altered placental microstructure.

Seasonal Variation of Chronic Villitis of Unknown Etiology.

INTRODUCTION: Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of the placenta. VUE is hypothesized to result from an alloimmune response or as response to an unidentified infection. Lack of a seasonal trend is thought to support VUE as an alloimmune response, though data on seasonal VUE trends are limited. METHODS: Data were obtained from a hospital in Chicago, Illinois, from 2011-2016. Placentas sent to pathology were reviewed using a standardized protocol, and VUE cases were identified based on an automated text search of pathology records. We used monthly VUE prevalence estimates to investigate the annual trend, and we used Poisson regression to evaluate seasonal variation in the number of VUE cases. RESULTS: There were 79 825 deliveries within the study period. Pathologists evaluated 12 074 placentas and identified 2873 cases of VUE. Regression results indicate that the risk of VUE is 16% to 17% higher in the fall and winter as compared to the summer (fall relative risk [RR]: 1.17, 95% confidence interval [CI]: 1.06-1.29; winter RR: 1.16, 95% CI: 1.05-1.29). DISCUSSION: Our results suggest that there may be seasonal variation in VUE prevalence, particularly for low-grade VUE. Future studies should evaluate seasonal variation in a representative sample rather than relying on pathology reports to estimate prevalence.

Recurrent Non Immune Fetal Hydrops Associated With IPEX Syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a clinical syndrome associated with mutations in FOXP3 and consequent abnormalities of T regulatory cells. Affected males typically die in infancy or early childhood from a variety of autoimmune conditions. Reports of recurrent pregnancy loss of male fetuses in these families have been accompanied by descriptions of nonimmune fetal hydrops, with or without additional fetal anomalies. Here, we report an additional family affected by IPEX with a novel mutation leading to recurrent second trimester fetal hydrops and intrauterine fetal demise with associated fetal anomalies. This report underscores how careful genetic and pathologic analysis of even midtrimester fetuses can provide important information impacting an entire family. It also further substantiates the use of broad, symptom-targeted genetic screening panels in cases of recurrent pregnancy loss even in the absence of a remarkable pedigree.

Occult Placenta Accreta: Risk Factors, Adverse Obstetrical Outcomes, and Recurrence in Subsequent Pregnancies.

OBJECTIVE: To assess the risk factors, adverse obstetrical outcomes, and recurrence risk associated with pathologically diagnosed occult placenta accreta. STUDY DESIGN: This was a retrospective observational study of clinically adherent placentas requiring manual extraction that underwent pathological examination. Cases were defined as those with histological evidence of placenta accreta, and controls were defined as those without accreta. All subsequent pregnancies were evaluated to determine the recurrence risk of occult accreta in future pregnancies. RESULTS: Of 491 women with clinically adherent placentas, 100 (20.1%) with a pathological diagnosis of occult accreta were compared with 391 (79.9%) without occult accreta. In bivariable analysis, risk factors associated with occult accreta included a history of previous cesarean (19 vs. 10.7%; p = 0.03) and prior uterine surgery (35 vs. 19.7%; p = 0.001). Adverse obstetrical outcomes were more common in women with occult accreta including postpartum hemorrhage (59 vs. 31.7%; p < 0.001) and peripartum hysterectomy (21 vs. 0.3%; p < 0.001). In 130 subsequent pregnancies, there was an increased risk of retained placenta (42.9 vs. 19%; p = 0.04) and recurrence of occult accreta (29.6 vs. 6.8%; p = 0.05). CONCLUSION: Occult accreta is associated with an increased risk of hemorrhagic morbidity and recurrence of morbidly adherent placenta in subsequent pregnancies.