Introduction: Spina bifida (SB) remains one of the most common congenital anomalies and associates with significant comorbidities in the fetus, which may, in part, be driven by placental maldevelopment. We hypothesised that placental pathologies would be more prevalent in fetuses with SB compared to fetuses without congenital anomalies.
Methods: Placental pathology and transcriptome were evaluated for fetuses with isolated open SB born preterm (cases; n = 12) and control fetuses without congenital anomalies (n = 22) born at full term (FT) or preterm (PT).
The placenta undergoes morphological and functional adaptations to adverse exposures during pregnancy. The effects ofsuboptimal maternal body mass index (BMI), preterm birth, and infection on placental histopathological phenotypes are not yet well understood, despite the association between these conditions and poor offspring outcomes. We hypothesized that suboptimal maternal prepregnancy BMI and preterm birth (with and without infection) would associate with altered placental maturity and morphometry, and that altered placental maturity would associate with poor birth outcomes.
View Article and Find Full Text PDFProblem: Fetal spina bifida (SB) is more common in pregnant people with folate deficiency or anomalies of folate metabolism. It is also known that fetuses with SB have a higher risk of low birthweight, a condition that is typically placental-mediated. We therefore hypothesized that fetal SB would associate with altered expression of key placental folate transporters and an increase in Hofbauer cells (HBCs), which are folate-dependent placental macrophages.
View Article and Find Full Text PDFIntroduction: Hypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR) are common obstetrical complications, often with pathological features of maternal vascular malperfusion (MVM) in the placenta. Currently, clinical placental pathology methods involve a manual visual examination of histology sections, a practice that can be resource-intensive and demonstrates moderate-to-poor inter-pathologist agreement on diagnostic outcomes, dependant on the degree of pathologist sub-specialty training.
Methods: This study aims to apply machine learning (ML) feature extraction methods to classify digital images of placental histopathology specimens, collected from cases of HDP [pregnancy induced hypertension (PIH), preeclampsia (PE), PE + FGR], normotensive FGR, and healthy pregnancies, according to the presence or absence of MVM lesions.
Placental pathology assessment following delivery provides an opportunity to identify the presence and type of disease that can mediate major obstetrical complications, especially in cases where the fetus is growth-restricted, born premature, or stillborn, or if the mother suffers from severe hypertensive morbidities [...
View Article and Find Full Text PDFIntroduction: Placental pathology is key for investigating adverse pregnancy outcomes, however, lack of standardization in reporting has limited clinical utility. We evaluated a novel placental pathology synoptic report, comparing its robustness to narrative reports, and assessed interobserver agreement.
Methods: 100 singleton placentas were included.
Maternal underweight and obesity are prevalent conditions, associated with chronic, low-grade inflammation, poor fetal development, and long-term adverse outcomes for the child. The placenta senses and adapts to the pregnancy environment in an effort to support optimal fetal development. However, the mechanisms driving these adaptations, and the resulting placental phenotypes, are poorly understood.
View Article and Find Full Text PDFPreeclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) in later life. Postpartum cardiovascular risk screening could identify patients who would benefit most from early intervention and lifestyle modification. However, there are no readily available methods to identify these high-risk women.
View Article and Find Full Text PDFExtremely preterm infants develop bronchopulmonary dysplasia (BPD), a chronic lung injury that lacks effective treatment. TSP-1 (thrombospondin-1) is an antiangiogenic protein that activates TGF-β1 (transforming growth factor-β1), a cytokine strongly linked to both experimental and human BPD. ) To examine effects of inhibiting TSP-1-mediated TGF-β1 activation (LSKL [leucine-serine-lysine-leucine]) in neonatal rats with bleomycin-induced lung injury; ) to examine effects of a TSP-1 mimic (ABT-510) on lung morphology; and ) to determine whether TSP-1 and related signaling peptides are increased in lungs of human preterm infants at risk for BPD.
View Article and Find Full Text PDFContext: Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition; however, few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected proinflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype.
View Article and Find Full Text PDFIntroduction: Neural tube defects (NTDs) are amongst the most common congenital anomalies and are associated with significant postnatal morbidity, but also with a higher incidence of low birthweight and fetal growth restriction. Despite the placenta being a critical determinant of fetal growth, placental development has not been extensively studied in fetuses with NTDs.
Methods: We performed a matched case-cohort study using data from the Collaborative Perinatal Project to assess the risk of placental pathology in pregnancies with an isolated fetal NTD (cases; n = 74) compared to those without any congenital anomalies (controls; n = 148).
Background: Necrotizing enterocolitis (NEC) is a major challenge for premature infants in neonatal intensive care units and efforts toward the search for indicators that could be used to predict the development of the disease have given limited results until now.
Methods: In this study, stools from 132 very low birth weight infants were collected daily in the context of a multi-center prospective study aimed at investigating the potential of fecal biomarkers for NEC prediction. Eight infants (~6%) received a stage 3 NEC diagnosis.
Preeclampsia is a multifactorial hypertensive disorder of pregnancy, with variable presentation in both maternal and fetal factors, such that no treatment or marker is currently universal to all cases. Here, we demonstrate that the prothrombinase and immunomodulatory secreted factor FGL-2 (fibrinogen-like protein 2) is differentially expressed across previously characterized gene expression clusters containing clinically relevant disease subtypes. is low in a cluster consistent with the traditional paradigm of the pathology of preeclampsia (canonical preeclampsia) and high in a cluster exhibiting evidence of immune activation (immunological preeclampsia).
View Article and Find Full Text PDFObjective: The objective of this study is to determine whether rapidity of death in necrotizing enterocolitis (NEC) increased odds of discordance between clinical and pathological diagnosis.
Study Design: Retrospective case-series study including preterm infants admitted to the NICU.
Results: Twenty-two infants met the selection criteria.
The use of inclusive terminology in health records continues to be a challenge for transgender, gender-diverse, and nonbinary peoples. When patients access electronic health records, laboratory results, including pathology reports, are among the most frequently viewed items. There has been limited discussion of transgender care within laboratory medicine, despite its role in providing written pathology reports after gender-affirming surgery.
View Article and Find Full Text PDFGastroschisis is a congenital abnormality characterized by visceral herniation through an abdominal wall defect. While the cause of gastroschisis is unknown, it has been linked to risk factors including young maternal age, smoking, and alcohol use during pregnancy. To date, the only established placental correlate is amniocyte vacuolization.
View Article and Find Full Text PDFOur prior work investigating the heterogeneity of preeclampsia identified multiple placental subtypes of this disorder, including a "canonical" group with maternal vascular malperfusion and an "immunological" group with signs of allograft rejection. Here, we perform a pilot immunohistochemistry study to investigate if an increase in infiltrating maternal immune cells is contributing to the "immunological" pathology subtype. This revealed an enrichment of monocytes and/or neutrophils (CD68 and MPO cells) in the intervillous space of these placentas.
View Article and Find Full Text PDFObjective: To report the clinical and variations in the histopathological features of pilomatrixoma of the ocular adnexa in 3 young individuals.
Design: A retrospective case series was performed with clinical, histological, and immunohistochemical analysis.
Participants: Case 1 is an 18-year-old male who presented with a reddish-blue swelling under the left eyebrow.
Statistically, patients with severe pregnancy complications are at risk of recurrent complications, but it is less understood if patients present with similar or different placental pathologies in subsequent pregnancies. In this case report, we describe 2 consecutive adverse pregnancies in the same woman 4 years apart. The first pregnancy was diagnosed as early-onset preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, with placental maternal vascular malperfusion features, such as syncytial knots and accelerated villous maturity.
View Article and Find Full Text PDFNeu-Laxova syndrome (NLS) is a lethal autosomal recessive microcephaly syndrome associated with intrauterine growth restriction (IUGR) and multiple congenital anomalies. Clinical features include central nervous system malformations, joint contractures, ichthyosis, edema, and dysmorphic facial features. Biallelic pathogenic variants in either the PHGDH or PSAT1 genes have been shown to cause NLS.
View Article and Find Full Text PDFPlacental pathology is a key modality for determining placental health during pregnancy, especially in the event of adverse pregnancy outcomes. However, issues with standardization in placental diagnosis, reporting practices and clinical translation prevent this modality from being used to its full potential. This article will highlight these standardization issues and summarize ongoing work in this field to overcome them.
View Article and Find Full Text PDFIntroduction: Accelerated placental maturation is considered a sign of maternal vascular malperfusion, and is often interpreted as an adaptive, compensatory response by the placenta. We tested this interpretation by comparing outcomes in pregnancies with and without accelerated maturation.
Methods: Using data from the National Collaborative Perinatal Project, we categorized preterm placentas (24-34 weeks, inclusive; 2525 births) by whether they showed placental villous hypermaturation (PVH), i.
Placental sexual dimorphism is of special interest in prenatal programming. Various postnatal diseases with gender dependent incidence, especially neuropsychiatric disorders like schizophrenia and autism spectrum disorders, have prenatal risk factors established. However, the functional relevance of placental microarchitecture in prenatal programming is poorly investigated, mainly due to a lack of statistically efficient methods.
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