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.

Mapping cell-to-tissue graphs across human placenta histology whole slide images using deep learning with HAPPY.

Accurate placenta pathology assessment is essential for managing maternal and newborn health, but the placenta's heterogeneity and temporal variability pose challenges for histology analysis. To address this issue, we developed the 'Histology Analysis Pipeline.PY' (HAPPY), a deep learning hierarchical method for quantifying the variability of cells and micro-anatomical tissue structures across placenta histology whole slide images. HAPPY differs from patch-based features or segmentation approaches by following an interpretable biological hierarchy, representing cells and cellular communities within tissues at a single-cell resolution across whole slide images. We present a set of quantitative metrics from healthy term placentas as a baseline for future assessments of placenta health and we show how these metrics deviate in placentas with clinically significant placental infarction. HAPPY's cell and tissue predictions closely replicate those from independent clinical experts and placental biology literature.

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.

Molecular detection of bacteria, placental inflammation, and neonatal sepsis risk.

OBJECTIVE: To identify bacteria in umbilical cord tissue and investigate the association with placental inflammation and neonatal sepsis risk score. STUDY DESIGN: Retrospective cohort study from 2017-2019. RNA was extracted from umbilical cord tissue and NanoString nCounter used to identify seven bacteria genera. Sepsis risk score was calculated using the Kaiser sepsis calculator. Placental histopathology was abstracted from medical records. RESULTS: Detection of bacterial RNA in the umbilical cord (n = 96/287) was associated with high-stage maternal and fetal acute placental inflammation (maternal 35.4% vs 22.5%, p = 0.03 and fetal 34.4% vs 19.4%, p < 0.01) and maternal vascular malperfusion (36.5% vs 23.0%, p = 0.02). Detection of Ureaplasma spp. was also associated with increased sepsis risk score (1.5/1000 [0.6, 8.6] vs 0.9/1000 [0.2, 2.9], p = 0.04). CONCLUSION: Umbilical cord bacterial pathogens are linked to fetal and maternal placental inflammation and maternal vascular malperfusion during gestation and associated with increased sepsis risk score in the neonate.

Inflammatory markers in serum and placenta in a randomized controlled trial of group prenatal care.

BACKGROUND: Racial and socioeconomic disparities in preterm birth and small for gestational age births are growing in the United States, increasing the burden of morbidity and mortality particularly among Black women and birthing persons and their infants. Group prenatal care is one of the only interventions to show potential to reduce the disparity, but the mechanism is unclear. OBJECTIVE: The goal of this project was to identify if group prenatal care, when compared with individual prenatal care, was associated with a reduction in systemic inflammation during pregnancy and a lower prevalence of inflammatory lesions in the placenta at delivery. STUDY DESIGN: The Psychosocial Intervention and Inflammation in Centering Study was a prospective cohort study that exclusively enrolled participants from a large randomized controlled trial of group prenatal care (the Cradle study, R01HD082311, ClinicalTrials.gov: NCT02640638) that was performed at a single site in Greenville, South Carolina, from 2016 to 2020. In the Cradle study, patients were randomized to either group prenatal care or individual prenatal care, and survey data were collected during the second and third trimesters. The Psychosocial Intervention and Inflammation in Centering Study cohort additionally provided serum samples at these 2 survey time points and permitted collection of placental biopsies for inflammatory and histologic analysis, respectively. We examined associations between group prenatal care treatment and a composite of z scored serum inflammatory biomarkers (C-reactive protein, interleukin-6, interleukin-1 receptor antagonist, interleukin-10, and tumor necrosis factor α) in both the second and third trimesters and the association with the prevalence of acute and chronic maternal placental inflammatory lesions. Analyses were conducted using the intent to treat principle, and the results were also examined by attendance of visits in the assigned treatment group (modified intent to treat and median or more number of visits) and were stratified by race and ethnicity. RESULTS: A total of 1256 of 1375 (92%) Cradle participants who were approached enrolled in the Psychosocial Intervention and Inflammation in Centering Study, which included 54% of all the Cradle participants. The Psychosocial Intervention and Inflammation in Centering Study cohort did not differ from the Cradle cohort by demographic or clinical characteristics. Among the 1256 Psychosocial Intervention and Inflammation in Centering Study participants, 1133 (89.6%) had placental data available for analysis. Among those, 549 were assigned to group prenatal care and 584 of 1133 were assigned to individual prenatal care. In the intent to treat and modified intent to treat cohorts, participation in group prenatal care was associated with a higher serum inflammatory score, but it was not associated with an increased prevalence of placental inflammatory lesions. In the stratified analyses, group prenatal care was associated with a higher second trimester inflammatory biomarker composite (modified intent to treat: B=1.17; P=.02; and median or more visits: B=1.24; P=.05) among Hispanic or Latine participants. CONCLUSION: Unexpectedly, group prenatal care was associated with higher maternal serum inflammation during pregnancy, especially among Hispanic or Latine participants.

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.

Comparison of Placental Pathology Reports From Spontaneous Preterm Births Finalized by General Surgical Pathologists Versus Perinatal Pathologist: A Call to Action.

Placental examination, frequently performed by general surgical pathologists, plays an important role in understanding patient outcomes and explaining the underlying mechanisms leading to preterm birth (PTB). This secondary analysis of a larger study recurrent PTB aimed to compare diagnoses between general surgical pathologists (GSP) and a perinatal pathologist (PP) in preterm placentas examined between 2009 and 2018 at a single institution. Pathology diagnoses were coded into 4 categories (acute inflammation [AI], chronic inflammation, fetal vascular malperfusion, maternal vascular malperfusion) based on original reports for the GSP and second review by the single PP. A total of 331 placentas were included, representing placentas finalized by 17 GSPs. The prevalence of all 4 placental diagnostic categories was higher for the PP, and nearly half (49.2%) of placentas finalized by GSP had no diagnostic findings. Agreement was highest for AI at κ=0.50 (weak agreement). However, there was no agreement for maternal vascular malperfusion (κ=0.063), chronic inflammation (κ=0.0026), and fetal vascular malperfusion (κ = -0.018). Chronic basal deciduitis with plasma cells had the highest false-negative rate (missed in 107 cases by GSP). Villous infarction had the highest false-positive rate (overcalled in 28/41 [68%] cases) with the majority of the "infarcts" representing intervillous thrombi. In conclusion, there is no agreement between GSP and PP when assessing placental pathology other than AI, and weak agreement even for AI. These findings are a call to action to implement educational efforts and structural/organizational changes to improve consistency of placental pathology reporting.

Patterns of placental pathology associated with preeclampsia.

INTRODUCTION: Maternal vascular malperfusion (MVM) is commonly observed in early onset preeclampsia, but less prevalent in late onset preeclampsia. The purpose of our analysis was to investigate patterns of placental pathology in preeclampsia. METHODS: Electronic health records for all singleton livebirths from 2009 to 2018 at a single institution with a diagnosis of preeclampsia were obtained. Text searching was used to obtain placental data from pathology reports, including lesions of MVM, fetal vascular malperfusion (FVM), chronic inflammation (CI), and acute inflammation (AI). Placental pathology was compared based on timing of delivery and latent class analysis (LCA) was used to investigate subtypes of preeclampsia based on 22 placental variables. RESULTS: 728 patients were included in the analysis. Prevalence of MVM decreased with advancing gestation (95.4% at <34 weeks, 69.8% at 34-36 weeks, and 50%, ≥37 weeks; p < 0.01). LCA identified five classes based on placental pathology: (1) high grade MVM, (2) CI and FVM, (3) low grade MVM, (4) AI, (5) other. Preterm birth varied across the classes (p < 0.01), with the highest prevalence observed among the classes characterized by MVM (high grade: 87.6%; low grade: 63.0%) and the lowest prevalence among the class characterized by AI (23.5%). DISCUSSION: Placental pathology in preeclampsia differs based on gestational age at delivery with MVM seen in nearly all early onset preeclampsia cases. Latent classes largely grouped by previously defined patterns of placental injury (MVM, CI, FVM, AI), and again revealed the highest likelihood of preterm birth in classes characterized by MVM. Results suggest there may be multiple mechanisms leading to the clinical manifestations of preeclampsia.

Low first-trimester fetal fraction is associated with chronic inflammation in the placenta.

BACKGROUND: Some data suggest an association between abnormal fetal fraction on noninvasive prenatal screening and adverse pregnancy outcomes, including low birthweight, preeclampsia, and preterm birth in the absence of aneuploidy. These findings suggest that abnormal fetal fraction may be associated with placental pathologic processes in early gestation. OBJECTIVE: This study aimed to determine the independent association of fetal fraction on genetic noninvasive prenatal screening with histologic placental types. STUDY DESIGN: This was a retrospective cohort study at a single institution in the period between January 2017 and March 2021, including live births at ≥24 weeks for which noninvasive prenatal screening was performed and placental pathology results were available. Results were stratified by trimester of noninvasive prenatal screening. Clinical characteristics were compared by quartile of fetal fraction using chi-square tests. Linear regression was used to model continuous fetal fraction as a function of 3 histologic types representing chronic placental injury-chronic inflammation, maternal vascular malperfusion, and fetal vascular malperfusion. Inverse probability weighting was used to account for selection bias in characteristics of patients with placental pathology examination. RESULTS: A total of 1374 patients had noninvasive prenatal screening in the first trimester and 262 in the second trimester. Preterm birth and hypertensive disorders of pregnancy were most common in the lowest quartile of fetal fraction. Chronic inflammation was associated with a 0.56 percentage point reduction in fetal fraction (95% confidence interval, -0.95 to -0.16), and maternal vascular malperfusion was associated with a 0.48 percentage point reduction in fetal fraction (95% confidence interval, -0.91 to -0.04) in adjusted models. The association with maternal vascular malperfusion was no longer statistically significant after accounting for selection bias in placentas sent for pathologic examination. Second-trimester fetal fraction was not associated with placental pathology. CONCLUSION: Chronic inflammation is associated with lower first-trimester fetal fraction even after accounting for selection bias. Higher fetal fraction in the second trimester was associated with fetal vascular pathology, although this association was no longer statistically significant after inverse probability weighting to account for selection bias. First-trimester fetal fraction may be a biomarker of adverse outcomes associated with chronic inflammation.

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.

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.

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.

The Prevalence of SARS-CoV-2 in Autopsies Surrounding the Time of Pandemic Onset: A Retrospective Review of Cases.

CONTEXT.­: The first case of COVID-19 in the United States was confirmed in January 2020. Initially, little was known about the epidemiology and clinical course of the disease, and diagnostic testing was limited in the United States until March/April 2020. Since then, many studies have speculated that SARS-CoV-2 may have preexisted undiagnosed outside China before the known outbreak. OBJECTIVE.­: To evaluate the prevalence of SARS-CoV-2 in adult autopsy cases performed just before and during the beginning of the pandemic at our institution, where autopsy was not performed on known COVID-19 cases. DESIGN.­: We included adult autopsies performed in our institution from June 1, 2019, to June 30, 2020. Cases were divided into groups based on the likelihood of cause of death being related to COVID-19, presence of a clinical respiratory illness, and histologic findings of pneumonia. Archived formalin-fixed, paraffin-embedded lung tissue of all COVID-possible cases and COVID-unlikely cases with pneumonia was tested for SARS-CoV-2 RNA, using Centers for Disease Control and Prevention 2019-nCoV quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS.­: Eighty-eight cases were identified, and among those, 42 (48%) were considered COVID-possible cause of death, with 24 of those 42 cases (57%) showing respiratory illness and/or pneumonia. COVID-19 as cause of death was considered unlikely in 46 of 88 cases (52%), with 34 of those 46 cases (74%) showing no respiratory illness or pneumonia. SARS-CoV-2 real-time reverse transcription-polymerase chain reaction was performed on a total of 49 cases, 42 COVID-possible and 7 COVID-unlikely with pneumonia, and all cases were negative (0 of 49). CONCLUSIONS.­: Our data suggest that autopsied patients in our community who died between June 1, 2019, and June 30, 2020, without known COVID-19 were unlikely to have had subclinical and/or undiagnosed COVID-19 infection.

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.

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.

Association of placental histology and neonatal hematologic outcomes.

OBJECTIVE: The objective of the paper was to investigate how neonatal hematologic outcomes vary by major placental histopathology categories. STUDY DESIGN: Placental pathology reports from 5263 subjects were coded into individual placental lesions. Infant hematologic data (complete blood count parameters (n = 1945), transfusions, and phototherapy) were compared by placental pathologic phenotype. RESULTS: Red blood cell transfusions were more likely with maternal vascular malperfusion (MVM; OR 9.4 [2.2, 40.8]) and chronic inflammation (1.7 [1.04, 2.7]). White blood cells were decreased with MVM (10.6 103/µL vs 16.4) and elevated with acute inflammation (AI; 18.6 vs 11.9). Thrombocytopenia was associated with MVM (OR 3.7 [2.2, 5.1]) and fetal vascular malperfusion (FVM; OR 2.6 [1.5, 4.6]). Platelet transfusions were more likely with MVM (OR 8.3 [4.6, 15.0]) and FVM (OR 2.9 [1.4, 6.1]). Phototherapy was associated with MVM (OR 3.3 [2.7, 4.0]) and AI (OR 0.8 [0.6, 0.9]). CONCLUSIONS: Neonatal hematologic outcomes are associated with the in utero environment described by placental pathology.

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.