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Placenta accreta spectrum is a life-threatening complication of pregnancy that is underdiagnosed and can result in massive hemorrhage, disseminated intravascular coagulation, massive transfusion, surgical injury, multisystem organ failure, and even death. Given the rarity and complexity, most obstetrical hospitals and providers do not have comprehensive expertise in the diagnosis and management of placenta accreta spectrum. Emergency management, antenatal interdisciplinary planning, and system preparedness are key pillars of care for this life-threatening disorder. We present an updated sample checklist for emergent and unplanned cases, an antenatal planning worksheet for known or suspected cases, and a bundle of activities to improve system and team preparedness for placenta accreta spectrum. [ABSTRACT FROM AUTHOR]

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect >75% of the placenta, effectively rendering it incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunologic basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death, the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis, and perinatal death. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is the most common respiratory sequela of prematurity, and infants born with fetal growth restriction (FGR) are disproportionately represented in BPD statistics, as factors which affect somatic growth may also affect pulmonary growth. Effects of in-utero hypoxia underlying FGR on lung parenchymal architecture predisposing to BPD are well documented, but the pulmonary vascular constructs are not well appreciated. Disruption of angiogenesis during critical periods of lung growth impairs alveolarization, contributing to BPD pathogenesis. Pulmonary artery thickness/stiffness has been noted in FGR in the initial postnatal weeks, and also in well-grown infants with established BPD. The lack of waveform cushioning by the major arteries exposes the pulmonary resistance vessels to higher pulsatile stress, thereby accelerating microvascular disease. Reactive oxygen species, increased sympathetic activity and endothelial dysfunction are common mediators in FGR and BPD; each putative targets for prevention and/or therapeutics using interleukin (IL)-1 receptor antagonist (IL-1Ra), melatonin or inhibition of renin–angiotensin–aldosterone system. While BPD is the archetypal respiratory disease of infancy, effects of FGR on pulmonary function are long-term, extending well into childhood. This narrative links FGR in very/extremely preterm infants with BPD through the vascular affliction as a mechanistic and potentially, therapeutic pathway. Our objectives were to depict the burden of disease for FGR and BPD amongst preterm infants, portray vascular involvement in the placenta in FGR and BPD cohorts, provide high resolution vascular ultrasound information in both cohorts with a view to address therapeutic relevance, and lastly, link this information with paediatric age-group lung diseases. [ABSTRACT FROM AUTHOR]

Introduction: Autopsy is regarded as the "gold standard" to determine probable causes of stillbirths. However, autopsy is expensive and not readily available in low- and middle-income countries. Therefore, we assessed how the clinical cause of death is modified by adding placental histology and autopsy findings.Method: Data from the Safe Passage Study was used where 7060 pregnant women were followed prospectively. Following a stillbirth, each case was discussed and classified at weekly perinatal mortality meetings. This classification was later adapted to the WHO ICD PM system. Clinical information was presented first, and a possible cause of death decided upon and noted. The placental histology was then presented and, again, a possible cause of death, using the placental and clinical information, was decided upon and noted, followed by autopsy information. Diagnoses were then compared to determine how often the additional information changed the initial clinical findings.Results: Clinical information, placental histology, and autopsy results were available in 47 stillbirths. There were major amendments from the clinical only diagnoses when placental histology was added. Forty cases were classified as due to M1: complications of placenta, cord, and membranes, when placental histology was added compared to 7 cases with clinical classification only, and M5: No maternal condition identified decreased from 30 cases to 3 cases. Autopsy findings confirmed the clinical and placental histology findings.Discussion: Clinical information together with examination of the placenta revealed sufficient information to diagnose the most probable cause of death in 40 of 47 cases of stillbirth (85%). [ABSTRACT FROM AUTHOR]

Introduction: Placental vascular disease, characterized by Maternal Vascular Malperfusion (MVM) lesions, is considered to be the underlying cause of pregnancy complications. Aim is to evaluate the relationship between the cumulative number of MVM lesion types, and adverse pregnancy- and neonatal outcomes.Methods: This retrospective cohort study included 272 women with singleton gestations who gave birth at a Dutch tertiary hospital between 2017 and 2018 with available placental histopathology reports. Analyzed according to the Amsterdam Placental Workshop Group Consensus Statement, placentas were divided into groups based on the cumulative number of MVM lesions: no lesions (n = 124), 1-2 types (n = 124) and 3-5 types of lesions (n = 24).Results: The proportion of placenta syndrome (PS) was highest (95.8%) in the 3-5 MVM lesions group (p < 0.001). The presence of MVM lesions was highly associated with PS during pregnancy (aOR 6.81, 95% CI 3.76-12.33). Furthermore, every additional type of MVM lesion corresponded with a threefold increased odds for the occurrence of PS (aOR 3.00, 95% CI 2.10-4.29). The group with 3-5 types of MVM lesions showed the highest incidence of adverse neonatal outcomes, lower mean birth weight, prolonged hospitalization, NICU admissions and neonatal deaths (aOR 6.47, 95% CI 0.33-127.68), corresponding with a fourfold increased odds for the occurrence of neonatal death for every additional MVM lesion (aOR 4.19, 95% CI 1.39-12.68).Discussion: A higher number of MVM lesion types is strongly associated with an increased incidence of adverse pregnancy- and neonatal outcomes, indicating that guidelines should focus also on the amount of MVM lesion types for the monitoring/management of subsequent pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: Villitis of unknown etiology (VUE) is associated with fetal growth restriction (FGR) and adverse short-term neonatal outcomes. No investigation to date has found which VUE features are driving the association with FGR diagnosis.Methods: A retrospective cohort study of placenta pathology specimens (2013-2017) was conducted. Independent variables of interest were: VUE distribution (focal vs diffuse), location (basal vs non-basal), and grade (high vs low). The primary outcome was FGR, and secondary outcomes were neonatal intensive care unit (NICU) admission, NICU length of stay, Apgar scores <7 at 1, 5, and 10-min, and recurrence rate of villitis in subsequent pregnancies. Association between VUE characteristics and our primary outcome were investigated using logistic regression. Secondary outcomes were explored with regression analyses and recurrence rate of VUE for members of the cohort with a recorded subsequent pregnancy was calculated.Results: One hundred and twenty seven placentas were included. Adjusted models showed no difference in the odds of FGR between high-grade versus low-grade VUE [aOR 1.25 95% CI (0.50, 3.26), p = 0.6], focal/multi-focal vs diffuse cases [aOR 1.03 95% CI (0.28, 4.34), p = >0.9], and basal vs non-basal VUE [aOR 0.06 95% CI (0.00, 1.10), p = 0.058]. After adjusting for prematurity <37 weeks, there were lower odds of NICU admission in basal vs non-basal cases [aOR 0.25, 95% CI (0.06, 0.90), p = 0.048). There was no difference in the odds of neonates presenting with Apgar <7 for the distinct VUE histopathology features. Three cases had recurrent VUE, resulting in a 6.8% [95% CI (3.02%, 10.61%)] recurrence rate. All recurrent cases were high-grade and identified with basal localization.Discussion: There are no statistical associations between distinct VUE features and FGR diagnosis, however location of villitis may be associated with worse neonatal outcomes. Villitis of any type (severity, degree, location) could potentially drive insufficient placental function and poor fetal growth. [ABSTRACT FROM AUTHOR]

Introduction: The pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the placenta, the interface between mother and baby during gestation. Sex-specific gene expression has been implicated in placental function, therefore, there is a need to determine if it is important during reduced fetal growth. We therefore aimed to characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants.Methods: RNA-sequencing of twelve human placental tissue samples collected from pregnancies yielding either term appropriate for gestational age (AGA) or SGA infants identified at delivery. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations.Results: Differential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. . Published placental sequencing datasets were used to validate the key expression results from the twelve placental samples initially studied; the sex-independent transcript expression for genes involved in cell cycle processes in males (7 transcripts) and endoplasmic reticulum stress in females (17 transcripts).Discussion: This study identified the activation of multiple molecular mechanisms involved in the placental response to an adverse environmental stressor. Mechanisms such as disrupted protein synthesis were shared between infant biological sex when comparing AGA to SGA, whilst other pathways such as cell cycle and endoplasmic reticulum stress appear as independent/specific to either males or females when investigating reduced fetal growth. This data suggests that sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth. [ABSTRACT FROM AUTHOR]

To study the relative importance of clinical and umbilical cord (UC) risk factors for placental fetal vascular malperfusion (FVM), 52 placentas with clinical UC compromise were compared with 204 placentas with other maternal/fetal conditions predisposing to FVM, 286 placentas with both factors, and 38 placentas with no clinical conditions or UC factors predisposing to FVM. FVM, both distal villous and global, was more common with UC compromise. Cases with isolated UC compromise were associated with more unfavorable clinical outcomes and histological distal FVM. Clinical conditions without umbilical cord compromise were not associated with increased rate of FVM. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a leading condition threatening pregnant women and their offspring. The offspring of PE pregnancies have a high risk of poor neurodevelopmental outcomes and neuropsychological diseases later in life. However, the pathophysiology and pathogenesis of poor neurodevelopment remain undetermined. Abnormal placental functions are at the core of most PE cases, and recent research evidence supports that the placenta plays an important role in fetal brain development. Here, we summarize the relationship between abnormal fetal brain development and placental dysfunction in PE conditions, which include the dysfunction of nutrient and gas-waste exchange, impaired angiogenesis stimulation, abnormal neurotransmitter regulation, disrupted special protectors, and immune disorders. All these factors could lead to poor neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Preeclampsia is a syndromic disease of the mother, fetus, and placenta. The main limitation in early and accurate diagnosis of preeclampsia is rooted in the heterogeneity of this syndrome as reflected by diverse molecular pathways, symptoms, and clinical outcomes. Gaps in our knowledge preclude successful early diagnosis, personalized treatment, and prevention. The advent of "omics" technologies and systems biology approaches addresses this problem by identifying the molecular pathways associated with the underlying mechanisms and clinical phenotypes of preeclampsia. Here, we provide a brief overview on how the field has progressed, focusing on studies utilizing state-of-the-art transcriptomics and proteomics methods. Moreover, we summarize our systems biology studies involving maternal blood proteomics and placental transcriptomics, which identified early maternal and placental disease pathways and showed that their interaction influences the clinical presentation of preeclampsia. We also present an analysis of maternal blood proteomics data which revealed distinct molecular subclasses of preeclampsia and their molecular mechanisms. Maternal and placental disease pathways behind these subclasses are similar to those recently reported in studies on the placental transcriptome. These findings may promote the development of novel diagnostic tools for the distinct subtypes of preeclampsia syndrome, enabling early detection and personalized follow-up and tailored care of patients. [ABSTRACT FROM AUTHOR]

Introduction: Chronic intervillositis of unknown etiology (CIUE) is a placental inflammatory process associated with pregnancy loss and high recurrence risk. The pathogenesis is unclear but involves aberrant maternal inflammation. This study assesses expression of inflammatory mediators by placenta and intervillus macrophage using digital spatial profiling, which is applicable to formalin fixed paraffin embedded tissue and provides whole transcriptome expression analysis at cellular resolution.Methods: Ethics approval was obtained and all experiments were performed in accordance with applicable guidelines and regulations. Archival tissue from early spontaneous pregnancy loss with high grade CIUE (4 cases) was compared to non-inflamed control normal placenta (4 cases) and granulomatous lymphadenitis as a macrophage inflammation control (4 cases). Differential gene expression between CIUE and relevant controls was assessed using unpaired t-test with Benjamini-Hochberg false discovery correction. Gene Set Enrichment Analysis (GSEA) was used to characterize and compare pathways active in the CIUE and relevant control samples.Results: Principal component analysis of the gene expression data showed distinct clustering with relatively little intragroup variation in the control tissues whereas the CIUE cases are more variable. Gene expression analysis showed changes in CIUE; however, no genes remained statistically significant after correction for false discovery. GSEA revealed prominent activation of IFN-related signaling pathways in CIUE placenta, particularly IFNγ signaling.Discussion: This study demonstrates that CIUE is associated with a specific profile of inflammatory mediators expressed by placenta villi that is dominated by IFN signaling, suggesting that uncontrolled IFNγ signaling may play a primary role in the pathogenetic mechanism underlying CIUE. [ABSTRACT FROM AUTHOR]

Introduction: To clarify the perinatal outcome of retained products of conception (RPOC) after 22 weeks or more.Methods: The retrospective cohort study reviewed medical records of patients with RPOC without placenta previa at 186 Japanese perinatal centers.Results: Of the 323 patients with RPOC, pregnancies after assisted reproductive technology (ART) accounted for 43%. Transfusion at delivery was required in 33% of the patients. Logistic regression analyses revealed that transfusion was significantly required in the following situations: ART pregnancy (aOR: 6.0, 95%CI: 2.3-16, P < 0.001), and RPOC length ≥4 cm (aOR: 5.3, 95%CI: 2.1-13, P < 0.001). Transarterial embolization (TAE) and/or hysterectomy for subsequent RPOC-related bleeding was performed in 60 patients with RPOC. Logistic regression analysis revealed that additional interventions were significantly required in the following situations: multiparity (aOR: 6.1, 95%CI: 2.1-17.2, P < 0.001), and hypervascular RPOC (aOR: 12.8, 95%CI: 3.2-51.1, P < 0.001). TAE and/or hysterectomy was also frequently employed in ART pregnancy, although this was not significant (aOR: 2.8, 95%CI: 0.9-8.2, P = 0.063).Discussion: Patients with RPOC were significantly more likely to require transfusion at delivery in the presence of large RPOC and ART. They were also more likely to require hemostatic procedures for subsequent bleeding in the presence of hypervascular RPOC and ART. [ABSTRACT FROM AUTHOR]

Copyright of Radiologia Brasileira is the property of Radiologia Brasileira and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (−282 stem villi; 95% confidence interval, −467 to −98; P <.01), a smaller stem villous area (−4.3 mm2; 95% confidence interval, −7.3 to −1.2; P <.01), and fewer stem villous vessels (−4967 stem villous vessels; 95% confidence interval, −8501 to −1433; P <.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (−873 terminal villi; 95% confidence interval, −1501 to −246; P <.01), the villous area (−1.5 mm2; 95% confidence interval, −2.7 to −0.4; P <.01), the number of blood vessels (−5165 terminal villous vessels; 95% confidence interval, −8201 to −2128; P <.01), and the vascular area (−0.6 mm2; 95% confidence interval, −1.1 to −0.1; P =.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Recurrence risk of villitis of unknown etiology (VUE) remains uncertain because of few studies and their methodologic limitations. We calculated recurrence risk in a large population of deliveries after minimizing important biases and compared it to others via systematic review and meta-analysis.Methods: Over 11 years of placenta pathology reports on singleton deliveries were retrieved and searched for 'villitis' or 'VUE'. Cases of acute villitis and chronic villitis from infections were eliminated via pathologist review. Reports were merged to data containing gestational age, parity and gravida. Recurrence risk of VUE per patient, per parity and per gravida was determined among patients with ≥2 placentas examined for deliveries ≥20 weeks gestation. Results were compared to those from articles and their references identified by a MEDLINE® search. Recurrence risks among methodologically similar studies were pooled using a random effects model.Results: Among 29 124 placenta pathology reports from 27 087 patients, there were 2423 cases of VUE among 2382 patients, of which 153 had ≥2 placentas examined. There were 41 recurrent cases of VUE for a recurrence risk of 27% per patient, 22% per parity, and 19% per gravida. We identified 64 articles, of which 4 were retained. One examined all placentas from all births over a ∼3-year period, finding a recurrence risk of 27%. The remaining 3 studies, along with our own, used indications for placental examination and had a pooled recurrence risk of 30% (95% Confidence Interval: 0.21-0.41).Discussion: In our study, which is the largest, most comprehensive, and methodologically robust to date, VUE recurrence risk was ∼30%. [ABSTRACT FROM AUTHOR]

The placenta is a highly metabolically active organ fulfilling the bioenergetic and biosynthetic needs to support its own rapid growth and that of the fetus. Placental metabolic dysfunction is a common occurrence in preeclampsia although its causal relationship to the pathophysiology is unclear. At the outset, this may simply be seen as an "engine out of fuel." However, placental metabolism plays a vital role beyond energy production and is linked to physiological and developmental processes. In this review, we discuss the metabolic basis for placental dysfunction and propose that the alterations in energy metabolism may explain many of the placental phenotypes of preeclampsia such as reduced placental and fetal growth, redox imbalance, oxidative stress, altered epigenetic and gene expression profiles, and the functional consequences of these aberrations. We propose that placental metabolic reprogramming reflects the dynamic physiological state allowing the tissue to adapt to developmental changes and respond to preeclampsia stress, whereas the inability to reprogram placental metabolism may result in severe preeclampsia phenotypes. Finally, we discuss common tested and novel therapeutic strategies for treating placental dysfunction in preeclampsia and their impact on placental energy metabolism as possible explanations into their potential benefits or harm. [ABSTRACT FROM AUTHOR]

Maternal tolerance of the semiallogenic fetus necessitates conciliation of competing interests. Viviparity evolved with a placenta to mediate the needs of the fetus and maternal adaptation to the demands of pregnancy and to ensure optimal survival for both entities. The maternal-fetal interface is imagined as a 2-dimensional porous barrier between the mother and fetus, when in fact it is an intricate multidimensional array of tissues and resident and circulating factors at play, encompassing the developing fetus, the growing placenta, the changing decidua, and the dynamic maternal cardiovascular system. Pregnancy triggers dramatic changes to maternal hemodynamics to meet the growing demands of the developing fetus. Nearly a century of extensive research into the development and function of the placenta has revealed the role of placental dysfunction in the great obstetrical syndromes, among them preeclampsia. Recently, a debate has arisen questioning the primacy of the placenta in the etiology of preeclampsia, asserting that the maternal cardiovascular system is the instigator of the disorder. It was the clinical observation of the high rate of preeclampsia in hydatidiform mole that initiated the focus on the placenta in the etiology of the disease. Over many years of research, shallow trophoblast invasion with deficient remodeling of the maternal spiral arteries into vessels of higher capacitance and lower resistance has been recognized as hallmarks of the preeclamptic milieu. The lack of the normal decrease in uterine artery resistance is likewise predictive of preeclampsia. In abdominal pregnancies, however, an extrauterine pregnancy develops without remodeling of the spiral arteries, yet there is reduced resistance in the uterine arteries and distant vessels, such as the maternal ophthalmic arteries. Proponents of the maternal cardiovascular model of preeclampsia point to the observed maternal hemodynamic adaptations to pregnancy and maladaptation in gestational hypertension and preeclampsia and how the latter resembles the changes associated with cardiac disease states. Recognition of the importance of the angiogenic-antiangiogenic balance between placental-derived growth factor and its receptor soluble fms-like tyrosine kinase-1 and disturbance in this balance by an excess of a circulating isoform, soluble fms-like tyrosine kinase-1, which competes for and disrupts the proangiogenic receptor binding of the vascular endothelial growth factor and placental-derived growth factor, opened new avenues of research into the pathways to normal adaptation of the maternal cardiovascular and other systems to pregnancy and maladaptation in preeclampsia. The significance of the "placenta vs heart" debate goes beyond the academic: understanding the mutuality of placental and maternal cardiac etiologies of preeclampsia has far-reaching clinical implications for designing prevention strategies, such as aspirin therapy, prediction and surveillance through maternal hemodynamic studies or serum placental-derived growth factor and soluble fms-like tyrosine kinase-1 testing, and possible treatments to attenuate the effects of insipient preeclampsia on women and their fetuses, such as RNAi therapy to counteract excess soluble fms-like tyrosine kinase-1 produced by the placenta. In this review, we will present an integrated model of the maternal-placental-fetal array that delineates the commensality among the constituent parts, showing how a disruption in any component or nexus may lead to the multifaceted syndrome of preeclampsia. [ABSTRACT FROM AUTHOR]

Objectives: Ischemic placental disease (IPD), including preeclampsia, abruption, and fetal growth restriction, often recurs in subsequent pregnancies. Angiogenic factors of placental origin have been implicated in the pathogenesis of preeclampsia, but have not been studied as predictors of IPD in subsequent pregnancies. We hypothesized that elevated angiogenic factors in an index pregnancy would be associated with recurrence of IPD.Study Design: We conducted a retrospective cohort study of patients undergoing evaluation for preeclampsia who had angiogenic factors measured in an index pregnancy and experienced a subsequent pregnancy at the same institution. Patients with IPD in the index pregnancy were included. A high ratio of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) was defined as greater than or equal to 85.Main Outcome Measures: The primary outcome was IPD in a subsequent pregnancy.Results: We included 109 patients in the analysis. The sFlt1/PlGF ratio was elevated in 30% of participants. Those with an elevated ratio were more likely to be nulliparous in the index pregnancy, and less likely to have chronic hypertension. The recurrence of IPD in the study was 27%, with a non-significant difference in risk based on a high sFlt-1/P1GF ratio RR 0.58 (95% CI 0.21 - 1.6) compared to a low ratio.Conclusions: A high sFlt1/P1GF ratio in an index pregnancy is not associated with a higher risk of IPD in a subsequent pregnancy. These data suggest placental angiogenic biomarkers are specific to the pregnancy and not a reflection of maternal predisposition to IPD. [ABSTRACT FROM AUTHOR]

Background: Elevated progesterone on the day of human chorionic gonadotropin (hCG) administration is associated with decreased live birth rates in IVF cycles. The association with adverse pregnancy outcomes is unknown.Objectives: Assess the association between serum progesterone on the day of hCG administration and the risk of ischemic placental disease [IPD; preeclampsia, placental abruption, and/or small for gestational age (SGA)].Methods: We conducted a retrospective cohort study of autologous fresh IVF cycles resulting in delivery between 2005 and 2018. All IVF procedures were conducted at a large, university-affiliated infertility center. Patients were divided into tertiles based on their serum progesterone level on the day of hCG administration; the lowest tertile served as the reference group. We identified pregnancies complicated by preeclampsia and placental abruption using ICD-9/10 codes and medical record review. We defined SGA as < 10th percentile using U.S. growth curves.Results: The cohort included 166 deliveries in the lowest tertile of progesterone (0.2-0.73 ng/ml), 166 deliveries in the middle (0.64-1.05 ng/ml) and 167 deliveries in the highest tertile (1.05-5.6 ng/ml). Compared with the lowest tertile, the risk of IPD was greater in the middle (RR 1.6; 95% CI 1.1-2.5) tertile after adjustment for age, parity, number of oocytes retrieved, and estradiol. The highest tertile was also not associated with an increased risk of IPD.Conclusion: In an IVF population, elevated serum progesterone in the range of 0.64-1.05 ng/mL on the day of hCG administration was associated with a small increased risk of IPD. [ABSTRACT FROM AUTHOR]

Copyright of Radiologia Brasileira is the property of Radiologia Brasileira and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Polypeptide hormones and steroid hormones, either expressed by the placenta or dependant on the placenta for their synthesis, are key to driving adaptations in the mother during pregnancy that support growth in utero. These adaptations include changes in maternal behaviour that take place in pregnancy and after the birth to ensure that offspring receive appropriate care and nutrition. Placentally-derived hormones implicated in the programming of maternal caregiving in rodents include prolactin-related hormones and steroid hormones. Neuromodulators produced by the placenta may act directly on the fetus to support brain development. A number of imprinted genes function antagonistically in the placenta to regulate the development of key placental endocrine lineages expressing these hormones. Gain-in-expression of the normally maternally expressed gene Phlda2 or loss-of-function of the normally paternally expressed gene Peg3 results in fewer endocrine cells in the placenta, and pups are born low birth weight. Importantly, wild type dams carrying these genetically altered pups display alterations in their behaviour with decreased focus on nurturing (Phlda2) or heightened anxiety (Peg3). These same genes may regulate placental hormones in human pregnancies, with the potential to influence birth weight and maternal mood. Consequently, the aberrant expression of imprinted genes in the placenta may underlie the reported co-occurrence of low birth weight with maternal prenatal depression. [ABSTRACT FROM AUTHOR]

Introduction: Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia.Methods: For 24 uncomplicated singleton pregnancies (gestational age 27-36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position. The maternal oxygenation was adjusted as 5 min of room air (21% O2), followed by 5 min of 100% FiO2. After datasets were corrected for signal non-uniformities and motion, global and regional BOLD signal changes in R2* and voxel-wise Time-To-Plateau (TTP) in the placenta were measured. The overall placental and uterine volume changes were determined across time to detect contractions.Results: In mothers without contractions, increases in global placental R2* in the supine position were larger compared to the left lateral position with maternal hyperoxia. Maternal position did not alter global TTP but did result in regional changes in TTP. 57% of the subjects had Braxton-Hicks contractions and 58% of these had global placental R2* decreases during the contraction.Conclusion: Both maternal position and Braxton-Hicks contractions significantly affect global and regional changes in placental R2* and regional TTP. This suggests that both factors must be taken into account in analyses when comparing placental BOLD signals over time within and between individuals. [ABSTRACT FROM AUTHOR]

The placenta, a temporary organ that forms during pregnancy, is the largest fetal organ and the first to develop. It is recognized as an organ that plays a vital role as a metabolic and physical barrier in the fetoplacental unit; throughout fetal development it acts as the lungs, gut, kidneys, and liver of the fetus. When its two components, the fetal and the maternal one, successfully interact, pregnancy proceeds healthily. However, in some cases there may be pregnancy disorders, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), which can lead to a different outcome for the mother and the newborn. In recent years, several studies have been conducted to try to understand how the expression of factors involved in the development of the placenta varies under pathological conditions compared with normal conditions. The purpose of this review is to summarize recent discoveries in this field. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to assess placental function by diffusion-weighted magnetic resonance imaging (MRI) using intravoxel incoherent motion (IVIM) analysis in uncomplicated pregnancies and pregnancies complicated by placental dysfunction.Methods: 31 normal pregnancies and 9 pregnancies complicated by placental dysfunction (birthweight ≤ -2SD and histological signs of placental vascular malperfusion) were retrieved from our placental MRI research database. MRI was performed at gestational weeks 20.1-40.6 in a 1.5 T system using 10 b-values (0-1000 s/mm2). Regions of interest were drawn covering the entire placenta in five transverse slices. Diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) were estimated by IVIM analysis.Results: In normal pregnancies, placental f decreased linearly with gestational age (r = -0.522, p = 0.002) being 26.2% at week 20 and 18.8% at week 40. D and D* were 1.57 ± 0.03 and 31.7 ± 3.1 mm2/s (mean ± SD), respectively, and they were not correlated with gestational age. In complicated pregnancies, f was significantly reduced (mean Z-score = -1.16; p = 0.02) when compared to the group of normal pregnancies, whereas D and D* did not differ significantly between groups. Subgroup analysis demonstrated that f was predominantly reduced in dysfunctional placentas characterized by fetal vascular malperfusion (mean Z-score = -2.11, p < 0.001) rather than maternal vascular malperfusion (mean Z-score = -0.40, p = 0.42). In addition, f was negatively correlated with uterine artery pulsatility index (r = -0.396, p = 0.01).Discussion: Among parameters obtained by the IVIM analysis, only f revealed significant differences between the normal and the dysfunctional placentas. Subgroup analysis suggests that placental f may be able to discriminate non-invasively between different histological types of vascular malperfusion. [ABSTRACT FROM AUTHOR]

Introduction: Chronic intervillositis of unknown etiology (CIUE) is a histopathological lesion of the placenta that is frequently accompanied by unfavourable pregnancy outcomes, e.g. miscarriage, fetal growth restriction (FGR) and intrauterine fetal death. Earlier described case series and cohorts have been based on diverse diagnostic criteria of CIUE. To improve our understanding of clinical outcomes associated with CIUE, we report the obstetric and perinatal outcomes in a cohort based on the recently described diagnostic criteria.Methods: CIUE is defined as an infiltrate occupying 5% or more of the intervillous space with approximately 80% of mononuclear cells positive for CD68 in the absence of an infection. Thirty-eight cases were included. Also previous and subsequent pregnancies were described.Results: Pregnancies accompanied by CIUE frequently resulted in FGR (51.6%) and pre-term birth (55.3%). Twenty-nine out of 38 pregnancies (76.3%) with CIUE resulted in a living baby. Women with CIUE frequently have had a miscarriage (16/38; 42%). Four-teen subsequent pregnancies in 8 women resulted in 2 miscarriages, 2 terminations of pregnancy for FGR, 1 early neonatal death and 9 living babies (9/14; 64.3%). Histopathologically confirmed CIUE recurred in 5 out of 10 subsequent pregnancies. Two pregnancies with recurrent CIUE were terminated, one pregnancy ended in a late miscarriage and another resulted in term birth complicated by FGR. Recurrent CIUE can also be accompanied by an uncomplicated pregnancy (1/5; 20%).Conclusion: This study provides additional insight into the clinical phenotype of CIUE and emphasises the need for further research to understand the pathophysiology behind different pregnancy outcomes in CIUE. [ABSTRACT FROM AUTHOR]

Introduction: Chronic histiocytic intervillositis (CHI) is a placental disease that has been associated with unfavorable obstetric outcomes in small, noncomparative series. The objective was to measure the excess risk of adverse obstetric outcomes associated with the discovery of CHI after birth.Methods: Retrospective single-center case-control study from 2000 through 2016. The case patients had a CHI diagnosis after a pathology analysis of the placenta. Two types of controls were defined for each case: low-risk control women were those who gave birth in our hospital immediately before each case patient, and the high-risk controls were the next women after each case for whom microscopic examination of the placenta was indicated.Results: We observed 111 cases of CHI during the study period. Compared with the 111 low-risk controls, the cases had a significantly higher frequency of late miscarriages (5.4 vs 0.0%, p < .03), small for gestational age (SGA) babies <3rd centile (70.4 vs 0.9%, p < .001, OR 140, 95% CI, 19.9-2800), and in utero deaths (35.1 vs 0.9%, p < .001, OR 59.6, 95% CI 8.5-1192), with significantly fewer children surviving to discharge (54.9 vs 99.1%, p < .001, OR 0.01, 95% CI, 0.00-0.08). All of these factors also differed significantly compared with the high-risk women (severe SGA: OR 3.7, 95% CI 1.9-7.0; in utero death: OR 4.1, 95% CI 1.9-8.7; children surviving to discharge: OR 0.27, 95% CI, 0.14-0.52).Discussion: Even compared with high-risk pregnancies, CHI is a severe placental disease associated with a substantial excess rate of late miscarriages, severe SGA and in utero death. [ABSTRACT FROM AUTHOR]

We sought to review the state of the science for research on multiple gestations. A literature search was performed with the use of PubMed for studies to quantify the representation of multiple gestations for a sample period (2012-2016) that were limited to phase III and IV randomized controlled trials, that were written in English, and that addressed at least 1 of 4 major pregnancy complications: fetal growth restriction or small-for-gestational-age fetus, gestational diabetes mellitus, preeclampsia, and preterm delivery. Of the 226 studies that are included in the analysis, multiple pregnancies were most represented in studies of preterm delivery: 17% of trials recruited both singleton and multiple pregnancies; another 18% of trials recruited only multiple pregnancies. For trials that studied preeclampsia, fetal growth restriction, and gestational diabetes mellitus, 17%, 8%, and 2%, respectively, recruited both singleton and multiple gestations. None of the trials on these 3 topics were limited to women with a multiple pregnancy. Women with a multiple pregnancy are at risk for complications similar to those of women with singleton pregnancies, but their risk is usually higher. Also, the pathophysiologic condition for some complications differs in multiple gestations from those that occur in singleton gestations. Conditions that are unique to multiple pregnancies include excess placenta, placental crowding or inability of the uteroplacental unit to support the normal growth of multiple fetuses, or suboptimal placental implantation sites with an increased risk of abnormal placental location. Other adverse outcomes in multiple gestations are also influenced by twin-specific risk factors, most notably chorionicity. Although twins have been well represented in many studies of preterm birth, these studies have failed to identify adequate predictive tests (short cervical length established over 2 decades ago remains the single best predictor), to establish effective interventions, and to differentiate the underlying pathophysiologic condition of twin preterm birth. Questions about fetal growth also remain. Twin growth deviates from that of singleton gestations starting at approximately 32 weeks of gestation; however, research with long-term follow-up is needed to better distinguish pathologic and physiologic growth deviations, which include growth discordance among pairs (or more). There are virtually no clinical trials that are specific to twins for gestational diabetes mellitus or preeclampsia, and subgroups for multiple pregnancies in existing trials are not large enough to allow definite conclusions. Another important area is the determination of appropriate maternal nutrition or micronutrient supplementation to optimize pregnancy and child health. There are also unique aspects to consider for research design in multiple gestations, such as designation and tracking of the correct fetus prenatally and through delivery. The correct statistical methods must be used to account for correlated data because multiple fetuses share the same mother and intrauterine environment. In summary, multiple gestations often are excluded from research studies, despite a disproportionate contribution to national rates of perinatal morbidity, mortality, and health-care costs. It is important to consider the enrollment of multifetal pregnancies in studies that target mainly women with singleton gestations, even when sample size is inadequate, so that insights that are specific to multiple gestations can be obtained when results of smaller studies are pooled together. The care of pregnant women with multiple gestations presents unique challenges; unfortunately, evidence-based clinical management that includes the diagnosis and treatment of common obstetrics problems are not well-defined for this population. [ABSTRACT FROM AUTHOR]

Abnormal placental invasion is associated with increased maternal morbidity and mortality. In an abnormally invasive placenta (AIP), the placental villi are not confined by the innate barrier of the uterine endometrium and invade the uterine myometrium and potentially even the uterine serosa. During the antenatal period, signs of abnormal invasion can be seen on ultrasound from as early as the first trimester. Typically, placental lacunae, a thin myometrium, abnormal blood flow in the placenta and myometrium, and/or an interrupted bladder edge should raise the clinical suspicion of AIP. Women with suspected AIP should be referred to centres with appropriate experience in the management of these cases, to optimize outcomes. Women are at significant risk of haemorrhage and other surgical complications. Therefore, skilled surgeons, anaesthetists and interventional radiologists should be involved in the planning and conduct of delivery of the baby. Some cases are not detected antenatally, only being recognized at the time of delivery. Appropriate assistance should be sought to plan and complete the delivery in these cases. [ABSTRACT FROM AUTHOR]

Introduction: In singletons, the pathogenesis of hypertensive disorders of pregnancy (HDP) is attributed to abnormal placentation, characterized by maternal vascular malperfusion (MVM) lesions. Whether MVM plays a similar role in twin pregnancies is unclear. The purpose of the study was to compared placental pathology findings between dichorionic-twin and singleton pregnancies complicated by HDP.Methods: Retrospective cohort study of women with dichorionic-twin or singleton pregnancies complicated by HDP who gave birth in a single tertiary center between 2001 and 2015. Placental abnormalities were classified into lesions associated with MVM, fetal vascular malperfusion, placental hemorrhage and chronic villitis. Placental findings and neonatal outcomes were compared between twin and singleton pregnancies.Results: A total of 144 women with twins and 768 women with a singleton pregnancy met the inclusion criteria. Compared with HDP singletons, twins with HDP had higher mean birth weights, were less likely to be small for gestational age and be born at <34 and at <32 weeks. Twins had lower odds for placental weight below <10th percentile (aOR 0.49, 95%CI 0.33-0.71), for MVM pathology (aOR 0.28, 95%CI 0.20-0.39) and for fetal vascular malperfusion pathology (aOR 0.65, 95%CI 0.45-0.93). These finding remained significant in the subpopulation of early onset HDP (<34 weeks) and small for gestational newborn.Discussion: Our findings support the hypothesis that MVM are less relevant to the pathogenesis of HDP in twin pregnancies and suggest that other placental or non-placental factors are responsible for the increased risk of HDP in twin pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: Chronic histiocytic intervillositis (CHI) of the placenta although rare, has a high recurrence rate, is associated with serious adverse pregnancy outcomes and has no available treatment. This study aims to determine clinical, biochemical and radiological factors associated with CHI, to guide management of subsequent pregnancies.Methods: This retrospective observational study included consecutive cases with a histopathologic diagnosis of CHI after 18 weeks of gestation, between 2001 and 2014, and no controls. Clinical (maternal, fetal and delivery outcomes), biochemical (first- and second-trimester biomarkers for fetal aneuploidy and serum alkaline phosphatase) and radiological (second- and third-trimester fetal, placental and Doppler ultrasound) factors associated with a histopathological diagnosis of CHI were identified and results presented as percentages. Outcomes of subsequent pregnancies were described.Results: Of 231 identified cases of 'intervillositis', 33 were confirmed to have CHI, of which only 4/33 (12.1%) had prior uncomplicated term deliveries. During pregnancy, 10/18 (55.5%) had abnormal first-trimester screening, 4/16 (25%) had abnormal second-trimester screening, 6/19 (31.6%) had at least one elevated alkaline phosphatase level, and 15/20 (75%) had at least one abnormal feature on mid-trimester placental ultrasound. In subsequent pregnancies that were closely followed with a combination of biochemical and radiologic tests, there were no cases of fetal loss, and lower incidence of fetal growth restriction and preterm birth.Discussion: No clinical, biochemical or radiological finding is consistently associated with CHI and adverse outcomes thereof. Whether the incorporation of these tests in individualized care-plans could improve outcomes in subsequent pregnancies needs to be studied further. [ABSTRACT FROM AUTHOR]

Placenta accreta spectrum is a complex obstetric complication associated with high maternal morbidity. It is a relatively new disorder of placentation, and is the consequence of damage to the endometrium-myometrial interface of the uterine wall. When first described 80 years ago, it mainly occurred after manual removal of the placenta, uterine curettage, or endometritis. Superficial damage leads primarily to an abnormally adherent placenta, and is diagnosed as the complete or partial absence of the decidua on histology. Today, the main cause of placenta accreta spectrum is uterine surgery and, in particular, uterine scar secondary to cesarean delivery. In the absence of endometrial reepithelialization of the scar area the trophoblast and villous tissue can invade deeply within the myometrium, including its circulation, and reach the surrounding pelvic organs. The cellular changes in the trophoblast observed in placenta accreta spectrum are probably secondary to the unusual myometrial environment in which it develops, and not a primary defect of trophoblast biology leading to excessive invasion of the myometrium. Placenta accreta spectrum was separated by pathologists into 3 categories: placenta creta when the villi simply adhere to the myometrium, placenta increta when the villi invade the myometrium, and placenta percreta where the villi invade the full thickness of the myometrium. Several prenatal ultrasound signs of placenta accreta spectrum were reported over the last 35 years, principally the disappearance of the normal uteroplacental interface (clear zone), extreme thinning of the underlying myometrium, and vascular changes within the placenta (lacunae) and placental bed (hypervascularity). The pathophysiological basis of these signs is due to permanent damage of the uterine wall as far as the serosa, with placental tissue reaching the deep uterine circulation. Adherent and invasive placentation may coexist in the same placental bed and evolve with advancing gestation. This may explain why no single, or set combination of, ultrasound sign(s) was found to be specific for the depth of abnormal placentation, and accurate for the differential diagnosis between adherent and invasive placentation. Correlation of pathological and clinical findings with prenatal imaging is essential to improve screening, diagnosis, and management of placenta accreta spectrum, and standardized protocols need to be developed. [ABSTRACT FROM AUTHOR]

Objective: Twin fetuses grow slower during the third trimester compared with singletons. However, the extent to which the relative smallness of twins is the result of placenta-mediated factors similar to those associated with fetal growth restriction in singletons remains unclear. Our aim was to address this question by comparing placental findings between small for gestational age (SGA) twins and SGA singletons.Methods: Retrospective cohort study of all SGA non-anomalous newborns from singleton and dichorionic twin pregnancies in a single tertiary referral center between 2002 and 2015. SGA was defined as birth weight <10th percentile for gestational age according to sex-specific national reference charts. Placental findings were compared between SGA twins and SGA singletons and were classified into lesions associated with maternal vascular malperfusion, fetal vascular malperfusion, placental hemorrhage and chronic villitis.Results: A total of 532 SGA twins and 954 SGA singletons met the inclusion criteria. SGA twins had a higher mean placental weight (371 ± 103 g vs. 319 ± 107, p < 0.001) and a lower fetal-placental ratio (6.0 ± 2.5 vs. 6.7 ± 3.2, p < 0.001) compared with SGA singletons. Compared with SGA singletons, SGA twins were less likely to have any placental pathology (aOR 0.37, 95%-CI 0.29-0.46), hypercoiled cord (aOR 0.45, 95%-CI 0.33-0.61), placental weight<10th% (aOR 0.13, 95%-CI 0.08-0.20), maternal vascular malperfusion pathology (aOR 0.24, 95%-CI 0.18-0.30) and fetal vascular malperfusion pathology (aOR 0.62, 95%-CI 0.48-0.82). By contrast, SGA twins had higher odds of a marginal or velamentous cord insertion compared with SGA singletons (aOR 13.82, 95%-CI 10.44-18.30). Similar significant associations were observed in subgroups of SGA fetuses with a birth weight below the 5th and 3rd percentile for gestational age.Conclusions: Our findings illustrate that the mechanisms underlying reduced fetal growth in dichorionic twins differ from those involved in singletons, and may provide support to the hypothesis that smallness in dichorionic twins may be more benign than in singletons. [ABSTRACT FROM AUTHOR]

In human pregnancy the maternal immune system plays a critical role in the regulation of many aspects of human reproduction including implantation, placentation and defence against infection. Interest has been focussed on the role of uterine natural killer cells (uNK) in the maternal decidua whereas effector CD4+ and CD8+ T cells have received much less attention despite the observation that they represent a major proportion of decidual leucocytes in the latter phase of pregnancy. A range of recent studies have demonstrated that human decidual T cells are highly differentiated, express a range of cytokines and cytotoxic markers, and demonstrate a unique transcriptional profile characterized by high level expression of genes involved in interferon-signalling. Moreover, subpopulations of effector T cells demonstrate specificity for fetal tissue and are regulated through expression of inhibitory checkpoint proteins and T regulatory cells. Nevertheless, many questions remain to be answered, such as the potential role of maternal effector T cells in either supporting successful pregnancy or potentially clearing fetal cells that have entered the maternal circulation. In addition, there is an increasing interest in the role of maternal effector T cells in the pathogenesis of disorders such as chronic villitis miscarriage, stillbirth, fetal growth restriction and pre-eclampsia. Current debates in relation to these questions will be discussed within this review. [ABSTRACT FROM AUTHOR]

Bidirectional transplacental exchange characterizes human pregnancy. Cells exchanged between mother and fetus can durably persist as microchimerism and may have both short- and long-term consequences for the recipient. The amount, type, and persistence of microchimerism are influenced by obstetric characteristics, pregnancy complications, exposures to infection, and other factors. A reproductive-aged woman enters pregnancy harboring previously acquired microchimeric "grafts," which may influence her preconception health and her subsequent pregnancy outcomes. Many questions remain to be answered about microchimerism with broad-ranging implications. This review will summarize key aspects of this field of research and propose important questions to be addressed moving forward. [ABSTRACT FROM AUTHOR]

Background: Novel measures of the chorionic plate and vessels are used to test the hypothesis that variation in placental structure is correlated with reduced birth weight (BW) independent of placental weight (PW), suggesting functionally compromised placentas.Methods: 916 mothers recruited to the Pregnancy, Infection and Nutrition Study delivering singleton live born infants at >30 gestational weeks had placentas collected, digitally photographed and weighed prior to formalin fixation. The fetal-placental weight ratio (FPR) was calculated as birthweight/placental weight. Beta (beta) was calculated as ln(PW)/ln(BW). Chorionic disk perimeter was traced and chorionic surface shape (CS) area was calculated. "Fit" was defined as the ratio of the area of the vascular to the full chorionic surface area. The sites at which chorionic vessels dived beneath the chorionic surface were marked to calculate the chorionic surface vessel (CV) area. The centroids of shapes, the distance between centroids and other measures of shape irregularities were calculated. Principal components analysis (PCA) created three independent factors. Factors were used in regression analyses to explore relations to birth weight, trimmed placental weight, FPR, and beta. Specific measures of shape irregularity were also examined in regression analyses for interrelationships and to predict birth weight, placental weight, FPR, and beta.Results: Variables related to disk size (CS area, perimeter) were correlated with BW, GA, trimmed PW and beta. "Fit" (the ratio of CV area to CS area), measures of shape irregularities, and the distance between the cord insertion and the centroids of surface and vascular areas were also correlated with one or more of the clinical outcome variables. PCA yielded three factors that had independent effects on birth weight, placental weight, the fetal-placental weight ratio, and beta (each p < 0.0001). Addition of GA did not alter the factors' associations with outcomes. Chorionic "fit" (ratio of areas), also included within the factor analysis, was a positive predictor of birth weight (p = 0.005) and FPR (p = 0.002) and a negative predictor of beta (p = 0.01). Fit was statistically significantly associated with greater distances between the umbilical cord insertion site and the CS (p < 0.001) and CV centroids (p < 0.001), and to lesser displacement between CS and CV centroids (p < 0.001).Conclusions: Measures of CS and CV account for variation in placental efficiency defined by beta, independent of GA. Macroscopic placenta measurements can identify suboptimal placental development. [ABSTRACT FROM AUTHOR]

Introduction: Research suggests that autism spectrum disorder (ASD) has its origins in utero. This study examines the association between evidence of placental histopathology and ASD.Methods: Administrative claims data and medical records data were used to identify ASD cases (N = 55) and matched controls (N = 199) born at New York Methodist Hospital between 2007 and 2014 and subsequently seen in affiliated pediatrics clinics. Placentas from all births during this time period were reviewed as part of routine care. Data were analyzed using conditional logistic regression to account for the matched (gender, gestational age, and birth weight) design.Results: Acute placental inflammation, regardless of type was associated with an increased risk of ASD (odds ratio [OR] = 3.14, 95% CI = 1.39, 6.95). Chronic uteroplacental vasculitis (OR = 7.13; 95% CI = 1.17, 43.38), the fetal inflammatory response in the chorionic plate vessels (OR = 5.12; 95% CI = 2.02, 12.96), and maternal vascular malperfusion pathology (OR = 12.29; 95% CI = 1.37, 110.69) were associated with an increased risk of ASD. Placental villous edema was associated with a decreased risk of ASD (OR = 0.05; 95% CI = 0.0005, 0.42). In subanalyses among male placentas acute inflammation overall, fetal inflammatory response in the chorionic plate vessels, and maternal vascular malperfusion pathology remained significantly associated with an increased risk of ASD whereas placental villous edema remained associated with a decreased risk of ASD.Discussion: Histologic evidence of placental inflammation and maternal vascular malperfusion pathology are associated with ASD. [ABSTRACT FROM AUTHOR]

Background: Women with a history of previous cesarean delivery, presenting with a placenta previa, have become the largest group with the highest risk for placenta previa accreta.Objective: The objective of the study was to evaluate the accuracy of ultrasound imaging in the prenatal diagnosis of placenta accreta and the impact of the depth of villous invasion on management in women presenting with placenta previa or low-lying placenta and with 1 or more prior cesarean deliveries.Study Design and Data Sources: We searched PubMed, Google Scholar, clinicalTrials.gov, and MEDLINE for studies published between 1982 and November 2016.Study Eligibility Criteria: Criteria for the study were cohort studies that provided data on previous mode of delivery, placenta previa, or low-lying placenta on prenatal ultrasound imaging and pregnancy outcome. The initial search identified 171 records, of which 5 retrospective and 9 prospective cohort studies were eligible for inclusion in the quantitative analysis.Study Appraisal and Synthesis Methods: The studies were scored on methodological quality using the Quality Assessment of Diagnostic Accuracy Studies tool.Results: The 14 cohort studies included 3889 pregnancies presenting with placenta previa or low-lying placenta and 1 or more prior cesarean deliveries screened for placenta accreta. There were 328 cases of placenta previa accreta (8.4%), of which 298 (90.9%) were diagnosed prenatally by ultrasound. The incidence of placenta previa accreta was 4.1% in women with 1 prior cesarean and 13.3% in women with ≥2 previous cesarean deliveries. The pooled performance of ultrasound for the antenatal detection of placenta previa accreta was higher in prospective than retrospective studies, with a diagnostic odds ratios of 228.5 (95% confidence interval, 67.2-776.9) and 80.8 (95% confidence interval, 13.0-501.4), respectively. Only 2 studies provided detailed data on the relationship between the depth of villous invasion and the number of previous cesarean deliveries, independently of the depth of the villous invasion. A cesarean hysterectomy was performed in 208 of 232 cases (89.7%) for which detailed data on management were available. Positive correlations were found in the largest prospective studies between the cumulative rates of the more invasive forms of accreta placentation and the sensitivity and specificity of ultrasound imaging but not with diagnostic odds ratio values. We found no data on the ultrasound screening of placenta accreta at the routine midtrimester ultrasound examination from the nonexpert ultrasound units.Conclusion: Planning individual management for delivery is possible only with accurate evaluation of prenatal risk of accreta placentation in women presenting with a low-lying placenta/previa and a history of prior cesarean delivery. Ultrasound is highly sensitive and specific in the prenatal diagnosis of accreta placentation when performed by skilled operators. Developing a prenatal screening protocol is now essential to further improve the outcome of this increasingly more common major obstetric complication. [ABSTRACT FROM AUTHOR]

Nutrient sulfate has numerous roles in mammalian physiology and is essential for healthy fetal growth and development. The fetus has limited capacity to generate sulfate and relies on sulfate supplied from the maternal circulation via placental sulfate transporters. The placenta also has a high sulfate requirement for numerous molecular and cellular functions, including sulfate conjugation (sulfonation) to estrogen and thyroid hormone which leads to their inactivation. Accordingly, the ratio of sulfonated (inactive) to unconjugated (active) hormones modulates endocrine function in fetal, placental and maternal tissues. During pregnancy, there is a marked increase in the expression of genes involved in transport and generation of sulfate in the mouse placenta, in line with increasing fetal and placental demands for sulfate. The maternal circulation also provides a vital reservoir of sulfate for the placenta and fetus, with maternal circulating sulfate levels increasing by 2-fold from mid-gestation. However, despite evidence from animal studies showing the requirement of maternal sulfate supply for placental and fetal physiology, there are no routine clinical measurements of sulfate or consideration of dietary sulfate intake in pregnant women. This is also relevant to certain xenobiotics or pharmacological drugs which when taken by the mother use significant quantities of circulating sulfate for detoxification and clearance, and thereby have the potential to decrease sulfonation capacity in the placenta and fetus. This article will review the physiological adaptations of the placenta for maintaining sulfate homeostasis in the fetus and placenta, with a focus on pathophysiological outcomes in animal models of disturbed sulfate homeostasis. [ABSTRACT FROM AUTHOR]

Background: Ultrasound (US) is the primary imaging modality for the diagnosis of placenta accreta, but it is not sufficiently accurate. MRI morphologic criteria have recently emerged as a useful tool in this setting, but their analysis is too subjective. Recent studies suggest that gadolinium enhancement may help to distinguish between the stretched myometrium and placenta within a scar area. However, objective MRI criteria are still required for prenatal diagnosis of placenta accreta. The purpose of this study was to assess the diagnostic value of dynamic contrast gadolinium enhancement (DCE) MRI patterns for placenta accreta.Materials and Methods: MR images were acquired with a 1.5-T unit at 30-35 weeks of gestation in women with a history of Caesarian section, a low-lying anterior placenta, and US features compatible with placenta accreta. Sagittal, axial and coronal SSFP (Steady State Free Precession) sequences were acquired before injection. Then, contrast-enhanced dynamic T1-weighted images were acquired through the entire cross-sectional area of the placenta. Images were obtained sequentially at 10- to 14-s intervals for 2 min, beginning simultaneously with the bolus injection. Functional analysis was performed retrospectively, and tissular relative enhancement parameters were extracted from the recorded images. The suspected area of accreta (SAA) was placed in the region of the previous scar, and a control area (CA) of similar size was placed on the same image plane, as far as possible from the SAA. Semi-quantitative analysis of DCE-MR images was based on the kinetic enhancement curves in these two regions of interest (ROI). Three tissular relative enhancement parameters were compared according to the pregnancy outcomes, namely time to peak, maximal signal intensity, and area under the enhancement curve.Results: We studied 9 women (43%) with accreta and 12 women (57%) with a normal placenta. All three tissular relative enhancement parameters differed significantly between the two groups (p < 10-3).Conclusion: The use of dynamic contrast-enhanced MRI at 30-35 weeks of gestation in women with a high risk of placenta accreta allows the extraction of tissular enhancement parameters that differ significantly between placenta accreta and normal placenta. It therefore provides objective parameters on which to base the diagnosis and patient management. [ABSTRACT FROM AUTHOR]

Introduction: Delayed villous maturation and accelerated villous maturation diagnosed in histologic sections are morphologic manifestations of pathophysiological conditions. The inter-observer agreement among pathologists in assessing these conditions is moderate at best. We investigated whether automated image analysis of placental villi and syncytial knots could improve standardization in diagnosing these conditions.Methods: Placentas of antepartum fetal death at or near term were diagnosed as normal, delayed or accelerated villous maturation. Histologic sections of 5 cases per group were photographed at ×10 magnification. Automated image analysis of villi and syncytial knots was performed, using ImageJ public domain software. Analysis of hundreds of histologic images was carried out within minutes on a personal computer, using macro commands.Results: Compared to normal placentas, villi from delayed maturation were larger and fewer, with fewer and smaller syncytial knots. Villi from accelerated maturation were smaller. The data were further analyzed according to horizontal placental zones and groups of villous size.Discussion: Normal placentas can be discriminated from placentas of delayed or accelerated villous maturation using automated image analysis. Automated image analysis of villi and syncytial knots is not equivalent to interpretation by the human eye. Each method has advantages and disadvantages in assessing the 2-dimensional histologic sections representing the complex, 3-dimensional villous tree. Image analysis of placentas provides quantitative data that might help in standardizing and grading of placentas for diagnostic and research purposes. [ABSTRACT FROM AUTHOR]

The connection between maternal hematological status and pregnancy outcome has been shown by many independent researchers. Attention was initially focused on the adverse effects of moderate and severe anemia. Interestingly, some studies revealed that mild anemia was associated with optimal fetal development and was not affecting pregnancy outcome. The explanation for this phenomenon became a target for scientists. Hemodilution, physiologic anemia and relative decrease in hemoglobin concentration are the changes observed during pregnancy but they do not explain the reasons for the positive influence of mild anemia on a fetomaternal unit. It is hypothesized that hemodilution facilitates placental perfusion because blood viscosity is reduced. Subsequently, it may lead to a decline in hemoglobin concentration. Anemia from its definition implies decreased oxygen carrying capacity of the blood and can result in hypoxemia and even hypoxia, which is a common factor inducing new blood vessels formation. Therefore, we raised the hypothesis that the lowered hemoglobin concentration during pregnancy may upregulate vascular growth factor receptors expression such as VEGFR-1 (Flt-1) and VEGFR-2 (FLK-1/KDR). Consecutively, increased fetoplacental vasculogenesis and angiogenesis provide further expansion of vascular network development, better placental perfusion and hence neither fetus nor the mother are affected. [ABSTRACT FROM AUTHOR]

Radiologic studies indicate that placental calcifications seen at 28-32 weeks' gestation are associated with adverse fetal outcome. One type of placental calcification is typically located at the basement membrane of chorionic villi. It has a fine particulate appearance and can only be seen microscopically. We have designated these calcifications as Intravillous and Intrafibrinous Particulate MicroCalcification (IPMC). In this study we examined the distribution and potential significance of IPMC. Placentas from 14 groups of fetal and maternal outcomes are examined histologically for IPMC. These groups were preterm birth, post term birth, intrauterine fetal demise, fetuses with non-reassuring heart rates, intrauterine growth restriction, fetal anomalies, mothers with gestational hypertension, gestational diabetes, placental abruption, pre-eclampsia and placentas of normal spontaneous vaginal births and placentas with chorioamnionitis, chronic villitis and infarcts. We observed fine dust-like particulates deposited in continuous and discrete patches. The particulates were predominantly located in the basement membranes of fibrotic chorionic villi and in perivillous fibrin. Compared to placentas without adverse outcomes, a higher incidence of IPMC was seen in intrauterine fetal demise cases and in cases with infarcts which suggests that hypoxia played a role in the etiology of IPMC. [ABSTRACT FROM AUTHOR]