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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]

Placental related disorders, including preeclampsia and fetal growth restriction (FGR) are among the main determinants of adverse maternal and perinatal outcomes in both singleton and twin pregnancies. In view of its relevance, aspirin administration is commonly recommended to women at high risk for preeclampsia or FGR by the various national and international guidelines. To establish the clinical heterogeneity among the clinical practice guidelines (CPGs) on aspirin use in pregnancy and to investigate the quality of these CPGs. We performed a systematic review of Clinical practice guidelines on main databases searching for all peer-reviewed guidelines into the literature, analyzing the following aspects related to use of aspirin in pregnancy: indications for aspirin administration, dosage, starting of therapy, ending of therapy, safety and side effects. The assessment of risk of bias and quality assessment of the included CPGs were performed using "The Appraisal of Guidelines for REsearch and Evaluation (AGREE II)" tool. 16 CPGs were included. There was an overall general agreement among the published CPGs as regards to the indication for aspirin intake in pregnancy, with prior preeclampsia, chronic hypertension, autoimmune disease, and diabetes mellitus type 1 or 2 recognized as solitary major risk factors for Aspirin administration in 93.7% (15/16) of CPGs. There was heterogeneity in the recommendations provided by the different CPGs as regards the gestational age at which aspirin should be commenced. There is general agreement in the reported indications for aspirin intake in pregnancy, with prior preeclampsia and maternal medical co-morbidity associated with increased risk of preeclampsia being the major indications for aspirin intake. Conversely, there was heterogeneity in the recommended dose, gestational age at initiation and discontinuation of therapy among the different CPGs. [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]

We aimed to generate a model to predict the risk of a woman having normal, abnormally adherent (AAP) or abnormally invasive placentation (AIP) based on the presence of recently codified ultrasound (US) markers and disease definitions of placenta accreta spectrum (PAS). We recruited women with anterior low-lying placenta or placenta previa and a history of previous caesarean delivery to a prospective cohort study. US markers of abnormal placentation were recorded on a standardized pro forma. The presence and International Federation of Gynecology and Obstetrics grade of PAS was evaluated clinically and histologically at delivery. Markers demonstrating a predictive relationship to PAS were incorporated into a logistic regression model. A total of 106 women were included, of whom 42 (40%) were normal, 24 (23%) had AAP and 40 (38%) had AIP. A model including just four key variables (loss of clear zone, abnormal placental lacunae, placental bulge and bladder wall interruption) was shown to reliably predict presence and severity of PAS, with an optimism-corrected C-index of 0.901. A simple model incorporating four US markers can predict likelihood and severity of PAS with high accuracy. This is the first time this has been demonstrated using the recently codified definitions of the US signs and disease definitions. Further work will see our model applied prospectively to a large patient cohort, ideally through a smartphone-based application, for external validation. [ABSTRACT FROM AUTHOR]

During pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR). Study design. This is a single institution, retrospective cohort study of patients ages 16–55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy. Among 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend). Asymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection. [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]

DNA mutations represent a hallmark of cancer. However, next-generation sequencing (NGS) approaches have revealed that similar somatic mutations are present in healthy tissues as well as in those of several diseases, aging, abnormal vascular formation, and in placental development. These findings call for a reappraisal of whether such mutations are pathognomonic for cancer and provide further mechanistic, diagnostic, and therapeutic implications. [ABSTRACT FROM AUTHOR]

Pregnancy complications such as pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are associated with structural and functional changes in the placenta. Different elastography techniques with an ability to assess the mechanical properties of tissue can identify and monitor the pathological state of the placenta. Currently available elastography techniques have been used with promising results to detect placenta abnormalities; however, limitations include inadequate measurement depth and safety concerns from high negative pressure pulses. Previously, we described a shear wave absolute vibro-elastography (SWAVE) method by applying external low-frequency mechanical vibrations to generate shear waves and studied 61 post-delivery clinically normal placentas to explore the feasibility of SWAVE for placental assessment and establish a measurement baseline. This next phase of the study, namely, SWAVE 2.0, improves the previous system and elasticity reconstruction by incorporating a multi-frequency acquisition system and using a 3-D local frequency estimation (LFE) method. Compared with its 2-D counterpart, the proposed system using 3-D LFE was found to reduce the bias and variance in elasticity measurements in tissue-mimicking phantoms. In the aim of investigating the potential of improved SWAVE 2.0 measurements to identify placental abnormalities, we studied 46 post-delivery placentas, including 26 diseased (16 IUGR and 10 PE) and 20 normal control placentas. By use of a 3.33-MHz motorized curved-array transducer, multi-frequency (80,100 and 120 Hz) elasticity measures were obtained with 3-D LFE, and both IUGR (15.30 ± 2.96 kPa, p = 3.35e-5) and PE (12.33 ± 4.88 kPa, p = 0.017) placentas were found to be significantly stiffer compared with the control placentas (8.32 ± 3.67 kPa). A linear discriminant analysis (LDA) classifier was able to classify between healthy and diseased placentas with a sensitivity, specificity and accuracy of 87%, 78% and 83% and an area under the receiver operating curve of 0.90 (95% confidence interval: 0.8-0.99). Further, the pregnancy outcome in terms of neonatal intensive care unit admission was predicted with a sensitivity, specificity and accuracy of 70%, 71%, 71%, respectively, and area under the receiver operating curve of 0.78 (confidence interval: 0.62-0.93). A viscoelastic characterization of placentas using a fractional rheological model revealed that the viscosity measures in terms of viscosity parameter n were significantly higher in IUGR (2.3 ± 0.21) and PE (2.11 ± 0.52) placentas than in normal placentas (1.45 ± 0.65). This work illustrates the potential relevance of elasticity and viscosity imaging using SWAVE 2.0 as a non-invasive technology for detection of placental abnormalities and the prediction of pregnancy outcomes. [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]

Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, −3 and −9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1high pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 high placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface. • Anti-angiogenic milieu induced by human soluble fms-like tyrosine kinase-1 (hsFLT1) alters the galectin-glycan circuits during pregnancy. • Decidual gal-1 is upregulated in hsFLT1 induced Preeclampsia (PE)-like syndrome in mice. • hsFLT1 exerts a strong influence on the O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation at the maternal-fetal interface. [ABSTRACT FROM AUTHOR]

Background: There is insufficient high-quality evidence to either support or discourage water birth (WB).Objectives: To examine different maternal complications of WB compared to standard land birth (LB). The primary outcomes were postpartum hemorrhage and genital trauma. The secondary outcome included the risk of retained placenta and shoulder dystocia.Methods: We searched the electronic databases including PubMed, MEDLINE, Embase, Scopus, EBSCO. In addition, we searched in Google Scholar and ClinicalTrials.gov. The pooled results were used to evaluate the association between WB and obstetric outcomes. This systematic review (SR) was reported according to PRISMA statement 2020. Statistical meta-analyses were performed using Cochrane RevMan version 5.4 software (http://www.cochrane.org).Results: This systematic review included 22 studies (20 observational studies and 2 RCT). The pooled results showed lower risk of major PPH compared to the LB group (OR = 0.76, 95% CI: 0.66-0.89), no significant difference (OR: 0.94, 95% CI: 0.50-1.78) in the incidence of minor PPH (500-1000 mL blood loss) between WB and LB, no significant difference in the rate of third- and fourth-degree lacerations (OR = 0.87, 95% CI: 0.71-1.07) and in the incidence of retained placenta (OR = 1.30, 95% CI: 0.50-3,35), fewer shoulder dystocia for WB (OR = 0.42, 95% CI: 0.35-0.50). However, compared with the LB group, the rate of first-second-degree tears in the WB group increased by 45% (OR = 1.45, 95% CI: 1.16-1.81).Conclusion: We support ACOG guidelines recommendation for further RCT to assess the impact of water immersion during delivery on maternal outcomes. [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]

Introduction: Growth discordancy in dichorionic diamniotic (DCDA) twin gestations is a known complication associated with adverse neonatal outcomes. We aimed to study the differences in placental pathology, in relation to fetal sex, in DCDA twin gestations complicated with growth discordancy.Methods: The medical files of all DCDA twin deliveries complicated by growth discordancy between 2010 and 2020 were reviewed. Growth discordance was defined as a gap between twin birthweights > 20%. A comparison was made between female vs. male growth discordant twins. Placental lesions were classified as lesions related to maternal or fetal malperfusion lesions (MVM, FVM), vascular and villous changes, and inflammatory lesions.Results: Included 174 DCDA twins. Eighty-eight were in the discordant female group and eighty-six in the discordant male group. The groups did not differ in maternal demographics, pregnancy characteristics, and neonatal outcome. The discordant male group had a higher rate of placental MVM lesions as compared to the discordant female group (p = 0.003). The increased rate of placental MVM lesions in the discordant male group compared to the discordant female group did not change whether its co-twin was of similar or opposite sex.Discussion: Higher rate of MVM lesions characterizes growth discordant male neonates in DCDA twin gestations. This finding could represent a different adaptation of male fetuses to a hostile intrauterine environment. [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]

We hypothesized isocaloric diets low in protein would decrease the sensitivity of caruncular (CAR) and cotyledonary (COT) arteries compared to placental arteries from ewes receiving adequate metabolizable protein (MP) requirements. Pregnant ewes were fed one of three isocaloric dietary treatments that provided 60% (MP60), 80% (MP80), or 100% (MP100) of the MP requirements. Diets were fed from day 100–130 of gestation. In vitro dose response curves to bradykinin (BK), sodium nitroprusside (SNP), potassium chloride (KCl), and phenylephrine (PE) in CAR and COT arteries were performed. As MP decreased, the sensitivity to a low dose of KCl increased (P = 0.05) in the COT arteries. There was an overall treatment effect in the CAR and COT arteries for the BK dose response curve, where CAR arteries of MP80 ewes were more sensitive (P = 0.05) to BK compared with MP60 and MP100 ewes, and COT arteries of MP60 and MP80 ewes were more sensitive (P = 0.01) to BK compared with MP100 ewes. There were no treatment effects (P ≥ 0.09) on the SNP or PE dose response curves in CAR or COT arteries. The mechanism of the BK induced vasodilation needs to be elucidated. Moreover, MP restriction appears to alter placental vascular function, which could help explain the differences in nutrient flux previously reported. [ABSTRACT FROM AUTHOR]

Objective: To compare placental pathology from term singleton live births conceived with fresh embryo transfer vs. those conceived without assisted reproductive technology (ART).Design: Retrospective cohort study.Setting: Academic fertility center.Patient(s): Women with a term singleton live birth who conceived after fresh autologous in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles (ART group) and those who conceived without ART.Intervention(s): An experienced placental pathologist categorized placental pathology as anatomic, inflammatory, or vascular. Patient characteristics were compared by chi-squared tests, Student's t-test, or nonparametric tests. Multivariate logistic regression models were used to compare placental pathology between pregnancies conceived with and without ART.Main Outcome Measure(s): Incidence of anatomic, inflammatory, and vascular placental pathology.Result(s): There was a higher incidence of placental pathology in the ART group (n = 511) than in the non-ART group (n = 121), specifically anatomic (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.42-4.40) and vascular (aOR 2.00, 95% CI 1.13-3.53) pathology. These findings were driven primarily by the significantly higher odds of anatomic (aOR 2.97, 95% CI 1.55-5.66) and vascular (aOR 1.98, 95% CI 1.04-3.75) pathology observed in ICSI pregnancies. Single blastocyst transfers remained associated with increased anatomic pathology (ART: aOR 4.89, 95% CI 2.28-10.49; ICSI: aOR 3.38, 95% CI 1.49-7.71).Conclusion(s): Fresh embryo transfer is associated with increased anatomic and vascular placental pathology in term singleton live births compared with conception without ART. This finding should be investigated prospectively in a larger cohort of patients. [ABSTRACT FROM AUTHOR]

While Malawi has made great strides increasing the number of facility-based births, maternal and neonatal mortality remains high. An intervention started in 2019 provided short-course training followed by year-long longitudinal bedside mentorship for nurse midwives at seven health facilities in Blantyre district. The intervention was initiated following invitation from the district to improve outcomes for patients during childbirth. This study examined the impact of the intervention on the reporting of obstetric and neonatal complications and related care. Patient level data were collected from the District Health Information System 2 database from intervention and non-intervention facilities. Bivariate analysis explored the impact of longitudinal bedside mentorship on select District Health Information System 2 variables at six-month intervals. Outcomes were then analyzed using nonlinear quantile mixed models to better account for the impact of time and clustering at the facility level. Significant changes were found in the reporting of obstetric and neonatal complications over time at intervention facilities compared to non-intervention facilities. Intervention facilities showed statistically significant increases in the reporting of prolonged labor, pre/eclampsia, fetal distress, retained placenta, and premature labor. There was also a statistically significant decrease in the reporting of no complications in the multivariate model (95%CI: − 0.8 to − 0.2). In both the bivariate and multivariate models, the reporting of 'None' significantly decreased (0.8 % median), while the reporting of prematurity (0.2 % median) and asphyxia (0.3 % median) both significantly increased. The missingness of data at intervention facilities decreased to almost zero compared to non-intervention facilities. The increase in reported maternal and neonatal complications suggests improved early identification of complications at the facility level. The improved accuracy of patient data from intervention facilities shows the impact mentorship has on data quality which is crucial for the allocation of resources. By highlighting the apparent dose–response relationship of longitudinal bedside mentorship, this study will inform the broader use of mentorship in training programs. Future research is needed to explore the impact of longitudinal mentorship on quality of care. [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]

Background: Identifying antepartum versus intrapartum timing and the cause of neonatal encephalopathy (NE) often remains elusive owing to our limited understanding of the underlying pathophysiological processes and lack of appropriate biomarkers.Objectives: This retrospective observational study describes a case series of term newborns with NE who displayed a recognizable magnetic resonance imaging pattern of immediately postnatal brain abnormalities that rapidly evolved toward cavitation. Our aim is to (1) report this neuroimaging pattern, (2) look for placental determinants, and (3) depict the outcome.Design/methods: This is a unicentric retrospective case series reporting the clinical, radiological, and laboratory findings of NE associated with a distinctive neuroimaging pattern, that is, immediately postnatal extensive corticosubcortical T2 hyperintensities, followed by rapid corticosubcortical cavitation that does not match the neuroimaging picture of intrapartum hypoxic-ischemic encephalopathy (HIE).Results: Seven term newborns presented bilateral corticosubcortical hyperintensities that were detected on T2 between day of life (DOL) 1-4, which rapidly evolved toward cystic encephalomalacia, that is, between DOL9 and DOL12. All these newborns presented with moderate/severe NE. The outcome was either neonatal death or quadriplegic cerebral palsy and epilepsy. None of the reported patients fulfilled the criteria of a high likelihood of acute intrapartum hypoxic-ischemic or quadriplegic cerebral palsy. All these newborns were exposed to chronic and/or acute placental inflammation and/or hypoxic-ischemic.Conclusions: To further define the antepartum causes of NE, early neuroimaging and a placental examination are recommended. Brain T2 hyperintense injuries before DOL4 followed by rapid cavitation before DOL12 might be biomarkers of NE from an antepartum/placental origin. [ABSTRACT FROM AUTHOR]

Driven by a lack of appropriate human placenta models, recent years have seen the introduction of bioengineered in vitro models to better understand placental health and disease. Thus far, the focus has been on the maternal–foetal barrier. However, there are many other physiologically and pathologically significant aspects of the placenta that would benefit from state-of-the-art bioengineered models, in particular, integrating advanced culture systems with contemporary biological concepts such as organoids. This critical review defines and discusses the key parameters required for the development of physiologically relevant in vitro models of the placenta. Specifically, it highlights the importance of cell type, mechanical forces, and culture microenvironment towards the use of physiologically relevant models to improve the understanding of human placental function and dysfunction. Advances in bioengineered microphysiological systems/organ-on-chip technologies provide in vitro models with greater physiological relevance and create opportunities to further investigate pregnancy and its complications. The complex and dynamic environment created by bioengineered models will likely provide significant new insights into placental function and dysfunction, especially when combined with contemporary biological concepts such as organoids. Bioengineered microphysiological models should be carefully tailored to address important specific physiological or pathological questions. [ABSTRACT FROM AUTHOR]

Placentitis is the leading cause of infectious abortion in the horse and contributes to roughly 19% of all abortions in the United States. A type of placental infection, nocardioform placentitis (NP) is associated with gram-positive branching actinomycetes localized within the ventral body of the feto-maternal interface to create a lymphoplasmacytic mucoid lesion. While the etiology of this disease is poorly described, this placental infection continues to cause episodic abortions in addition to weak and/or growth retarded neonates. The goal of the present study was to perform a comprehensive analysis of pregnancies associated with a nocardioform-affected placenta and make inferences into the epidemiology of this elusive disease. To do so, 264 mares were enrolled in the study, with 145 as having suspected disease (n = 145; NP) either based on pregnancy-related complications or postpartum placental evaluation, while an additional 119 were enrolled as healthy pregnancies (n = 119; CON). Following diagnosis as either NP or CON based on gross and histopathology at the University of Kentucky Veterinary Diagnostic Laboratory, information was gathered on the mares and neonates for comparisons between diseased and healthy pregnancies. Clinically, a significant portion of diseased mares had clinical indications of NP, including premature mammary gland development, thickening of the placenta noted on transrectal ultrasonography, and separation between the chorioallantois and endometrium noted on abdominal ultrasonography, while vulvar discharge was not commonly noted. Additionally, NP was correlated with increased mare age, decreased gestational length, and decreased neonatal weight, although neonatal IgG and WBC were comparable to CON. Incidence of NP was not correlated with last breeding date, pre- and post-breeding therapeutics, parity, prophylactic medications, or housing. Additionally, NP did not affect postpartum fertility. While NP was associated with a poor neonatal outcome (abortion and/or growth retarded neonate), this did not appear to be influenced by the bacteria isolated (Amycolatopsis spp. vs. Crossiella equi), and mares diagnosed with NP do not appear to be infectious to other pregnant mares nor have repetitive years of the disease. Interestingly, lesion size was positively correlated with last breeding date, as mares bred later in the breeding season correlating with a larger placental lesion. In conclusion, while the etiology of NP continues to elude researchers, the epidemiology of this disease has gained clarity, providing inferences into the management of suspect mares. • NP was associated with increased mare age but had no correlation with parity, last breeding date, or postpartum fertility. • NP was associated with dead or growth retarded neonates, but foals born alive were otherwise clinically normal. • Focal mucoid lesion size was positively correlated with last breeding date, as mares bred later in the season were associated with a larger lesion size. • Prophylactic administration of progestins and/or antibiotics did not decrease the disease acquisition of NP. [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: We evaluated the rates of placental pathologic lesions and their relationship with two-year neurodevelopmental outcomes in very-low-birth-weight (VLBW) infants.Methods: This is a cohort observational study comprising 595 VLBW infants during 2007 to 2015. Neurodevelopmental assessment was carried out at 24 months corrected age.Results: In univariate analysis the rates of survival with normal neurodevelopmental outcomes were lower in pregnancies with severe histologic chorioamnionitis (38 of 43, 88.4% when compared with 305 of 450, 67.8%), severe maternal vascular malperfusion (MVM) (17 of 37, 45.9% when compared with 326/492, 66.3%), and intravillous hemorrhage (37 of 82, 45.1% when compared with 306 of 449, 68.1%). In logistic models, severe MVM (adjusted odds ratio [adj. OR] = 0.45, 95% confidence interval [CI] = 0.22 to 0.92), severe fetal vascular malperfusion (FVM) (adj. OR = 0.46, 95% CI = 0.22 to 0.45), and intravillous hemorrhage (adj. OR = 0.38, 95% CI = 0.22 to 0.62) were associated with lower rates of infant survival with normal neurodevelopmental outcome. FVM (adj. OR = 0.46, 95% CI = 0.21 to 0.97) and intravillous hemorrhage (adj. OR = 0.37, 95% CI = 0.22 to 0.62) were also the only placental lesions that were independent predictors of a lower rate of intact survival in stepwise analysis for prognostic factors of the entire cohort.Conclusions: Placental pathologic findings such as severe MVM, FVM, and intravillous hemorrhage are significant predictors of neonatal survival and subsequent adverse neurodevelopmental outcomes. Data on the placental pathology could be useful in the neurodevelopmental follow-up of VLBW infants. [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]

Background: The pandemic of the severe acute respiratory distress syndrome-associated Coronavirus-2 (SARS-CoV-2) has affected millions around the world. In pregnancy the dangers to the mother and fetus are still being explored. SARS-CoV2 can potentially compromise maternal and neonatal outcomes and this may be dependent on the pregnancy stage during which the infection occurs.Objective: The present study was done to find the histopathological alterations in the placenta of SARS-CoV-2 positive pregnancies with either no symptoms or mild coronavirus disease (COVID)-19 related symptoms and its association with neonatal outcomes.Study Design: This was a prospective analytical study. Twenty seven asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women with a singleton pregnancy delivered between 1st July 2020 and 15th September 2020, were included as cases. An equal number of SARS-CoV-2 negative singleton pregnancies matched for maternal and gestational age during the same period were included as controls. After delivery the histopathological examination of the placenta of these women was done and the findings recorded on a predesigned proforma based on the Amsterdam consensus criteria for evidence of maternal and fetal vascular malperfusion changes.Results: The baseline characteristics were comparable between the cases and controls. The following features of maternal vascular malperfusion (MVM) were significantly higher in the placentae of COVID-19 positive pregnancies: retroplacental hematomas (RPH), accelerated villous maturation (AVM), distal villous hyperplasia (DVH), atherosis, fibrinoid necrosis, mural hypertrophy of membrane arterioles (MHMA), vessel ectasia and persistence of intramural endovascular trophoblast (PIEVT). Fetal vascular malperfusion (FVM) significantly associated with the positive pregnancies were chorioangiosis, thrombosis of the fetal chorionic plate (TFCP), intramural fibrin deposition (IMFD) and vascular ectasia. Additionally, perivillous fibrin deposition was also significantly higher in the placentae of cases. The percentage of spontaneously delivered women was comparable in the two groups. The sex and weight of the newborn and the number of live births were comparable between the two groups.Conclusions: Asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women, with otherwise uncomplicated pregnancies, show evidence of placental injury at a microscopic level. Similar findings have been demonstrated in other studies too. This placental injury apparently does not lead to poor pregnancy outcomes. The extent of this injury in symptomatic cases of COVID-19 pregnancies and its consequences on the outcomes need to be analysed. [ABSTRACT FROM AUTHOR]

The objective of the current study was to evaluate the relationship of body condition score (BCS) at 35 d in milk (DIM), milk production, diseases, and duration of the dry period with prevalence of anovulation at 49 DIM and then, specifically, with the prevalence of each anovular phenotype. We hypothesized that anovular follicular phenotypes, classified based on maximal size of the anovular follicle, have different etiologies. A total of 942 lactating Holstein cows (357 primiparous and 585 multiparous) from 1 herd had ovaries evaluated by ultrasonography at 35 ± 3 and 49 ± 3 DIM to detect the absence of a corpus luteum (CL), and to measure the diameter of the largest follicle. Cows were classified as cyclic at 49 DIM if a CL was observed in at least 1 of the 2 examinations, or anovular if no CL was observed at either examination. Cows considered anovular were divided into 3 groups based on the largest diameter of the largest follicle as follows: ranging from 8 to 13 mm, 14 to 17 mm, or ≥18 mm. Cows were evaluated for the following diseases: retained placenta, metritis, hyperketonemia, mastitis, lameness, respiratory problem, and digestive problem. At 35 DIM, BCS was determined, and milk yield for individual cows was recorded. A total of 28.5% (268/942) of cows were classified as anovular. Anovular cows had longer dry periods (90 vs. 71 d) and smaller BCS than cyclic cows (2.83 vs. 2.99). Cows with a single disease or multiple diseases had 2 and 3-fold increase in odds of being anovular, respectively. Anovular cows had follicles that ranged from 4 to 50 mm. The prevalence of anovular phenotype, among anovular cows, that had the diameter of the largest follicle ranging from 8 to 13 mm, 14 to 17 mm, and ≥18 mm was 29.9 (79/264), 37.5 (99/264), and 32.6% (86/264), respectively. Anovular cows with follicles of 8 to 13 mm had longer dry periods than those with follicles ≥18 mm (104 vs. 74 d), whereas anovular cows with medium size follicles had intermediate days dry (99 d). Cows with small and medium anovular follicles had smaller BCS and greater prevalence of multiple diseases than cyclic cows. For almost all risk factors, the cows with large anovular follicles (≥18 mm) were similar to cyclic cows and different from cows with smaller anovular follicles (8–13 mm). Thus, longer dry periods, less BCS at 35 DIM, and diseases were risk factors for anovulation. Moreover, the risk factors for the 3 distinct anovular follicle phenotypes differed. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the development of placental vascularization in normal gestation by using Doppler superb microvascular imaging (SMI). The fetal and maternal parameters of 20 pregnant women without pathology were evaluated at weeks 12, 16, 20-22, 24-26, 28-30, 32-34, 36-38 and 40-42. Doppler SMI was used to evaluate the placental vascularization (pulsatile index and peak systolic velocity) of the primary, secondary and tertiary (third) villi, and qualitative placental descriptions and anatomic-pathologic studies of these placentas were performed. The number of cotyledons identified by Doppler SMI increased from two between weeks 16 and 18 to 24 between weeks 28 and 38. The secondary and tertiary villi began developing at 20 wk of gestation. The pulsatile index of the primary villi remained constant (0.8-0.9 in all pregnancies). The pulsatile index of the secondary and tertiary villi increased from 1.1 to 1.53 and from 1.4 to 1.68, respectively. The peak systolic velocity underwent a significant increase throughout gestation in the secondary and tertiary villi (9.2 to 34.9 cm/s and 7.5 to 52.9 cm/s, respectively). We evaluated the development of placental microvascularization using Doppler SMI in pregnancies without pathology and describe normal placental Doppler SMI findings. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between in vitro fertilization (IVF) and ischemic placental disease (IPD), stratified by gestational age.Design: We performed a secondary analysis of a retrospective cohort study of deliveries.Setting: Deliveries were performed over 15 years at a single tertiary hospital.Patient(s): We included all parturients who had a live born infant or an intrauterine fetal demise (IUFD).Intervention(s): We compared pregnancies resulting from IVF cycles to non-IVF pregnancies.Main Outcome Measure(s): The primary outcomes were preterm and term IPD (preeclampsia, placental abruption, small-for-gestational age infant [SGA], or an intrauterine fetal demise [IUFD] due to placental insufficiency).Result(s): Of the 69,084 deliveries during the study period, 3,763 (5.4%) were conceived with IVF. The incidence of preterm delivery was 32.6% in IVF pregnancies and 10.8% in non-IVF pregnancies. Multiple gestations were more common in IVF pregnancies. Compared to non-IVF pregnancies, IVF pregnancies were more likely to develop both preterm and term IPD, even after adjustment for maternal age and parity. The risk of preterm IPD was 4 times higher (95% confidence interval, 3.7-4.4) in patients who underwent IVF compared with those who did not undergo IVF. Among parturients who delivered at ≥37 weeks of gestation, IVF pregnancies had 1.7 times the risk of term IPD (95% confidence interval, 1.6-1.9) compared with non-IVF pregnancies.Conclusion(s): IVF was strongly associated with preterm IPD. We found a similar, but attenuated, association between IVF and term IPD. The stronger association with preterm IPD suggests an association between IVF and placental insufficiency. [ABSTRACT FROM AUTHOR]

Introduction: Among SGA newborns, those < 5th % for GA are more likely to have adverse outcomes than those at 5-9th %. The differential morbidity and mortality may be due to abnormal placental pathology between groups. Our purpose was to compare placental pathology characteristics and composite placental pathology among SGA infants with birth weights <5th % vs. 5-9th %.Methods: This study is a secondary analysis of a multicenter, retrospective cohort study. Placental pathological variables and composite placental pathology (CPP) among SGA infants <5th % and 5-9th % were compared. Multivariable logistic regression was used to model the probability of an infant's birth weight being classified as <5th % based on pathology characteristics.Results: Of 11,487 live singleton births, 925 SGA infants met inclusion criteria. Placental pathology was available for review in 407 (44 %) SGA infants: 210 (51.6 %) <5th % and 197 (48.4 %) 5-9th %. A decreased placental weight for GA, was more common in the <5th % group compared to the 5-9th % group (p = 0.0019). No significant differences in the distribution of pathological variables or in CPP (p = 0.3) was observed between the two centile groups. A decreased placental weight was the only reliable predictor of an infant's birth weight centile group (p = 0.0018).Conclusions: Placental hypoplasia, reflected by a decreased placental weight for GA, was significantly more common among SGA infants < 5th % compared to the 5-9th %. There was no difference in placental pathological features or CPP between the two centile groups of SGA infants. [ABSTRACT FROM AUTHOR]

Objective: To investigate the outcome of pregnancies with small baby, including both small for gestational age (SGA) and late fetal growth restriction (FGR) fetuses, undergoing induction of labor (IOL) with Dinoprostone, Misoprostol or mechanical methods.Study Design: Medline, Embase and Cochrane databases were searched. Inclusion criteria were non-anomalous singleton pregnancies complicated by the presence of a small fetus, defined as a fetus with estimated fetal weight (EFW) or abdominal circumference (AC) <10th centile undergoing IOL from 34 weeks of gestation with vaginal Dinoprostone, vaginal misoprostol, or mechanical methods (including either Foley or Cook balloon catheters). The primary outcome was a composite measure of adverse intrapartum outcome. Secondary outcomes were the individual components of the primary outcome, perinatal mortality and morbidity. All the explored outcomes were reported in three different sub-groups of pregnancies complicated by a small fetus including: all small fetuses (defined as those with an EFW and/or AC <10th centile irrespective of fetal Doppler status), late FGR fetuses (defined as those with EFW and/or AC <3rd centile or AC/EFW <10th centile associated with abnormal cerebroplacental Dopplers) and SGA fetuses (defined as those with EFW and/or AC <10th but >3rd centile with normal cerebroplacental Dopplers). Quality assessment of each included study was performed using the Risk of Bias in Non-randomized Studies-of Interventions tool (ROBINS-I), while the GRADE methodology was used to assess the quality of the body of retrieved evidence. Meta-analyses of proportions and individual data random-effect logistic regression were used to analyze the data.Results: 12 studies (1711 pregnancies) were included. In the overall population of small fetuses, composite adverse intra-partum outcome occurred in 21.2 % (95 % CI 10.0-34.9) of pregnancies induced with Dinoprostone, 18.0 % (95 % CI 6.9-32.5) of those with Misoprostol and 11.6 % (95 % CI 5.5-19.3) of those undergoing IOL with mechanical methods. Cesarean section (CS) for non-reassuring fetal status (NRFS) was required in 18.1 % (95 % CI 9.9-28.3) of pregnancies induced with Dinoprostone, 9.4 % (95 % CI 1.4-22.0) of those with Misoprostol and 8.1 % (95 % CI 5.0-11.6) of those undergoing mechanical induction. Likewise, uterine tachysystole, was recorded on CTG in 13.8 % (95 % CI 6.9-22.3) of cases induced with Dinoprostone, 7.5 % (95 % CI 2.1-15.4) of those with Misoprostol and 3.8 % (95 % CI 0-4.4) of those induced with mechanical methods. Composite adverse perinatal outcome following delivery complicated 2.9 % (95 % CI 0.5-6.7) newborns after IOL with Dinoprostone, 0.6 % (95 % CI 0-2.5) with Misoprostol and 0.7 % (95 % CI 0-7.1) with mechanical methods. In pregnancies complicated by late FGR, adverse intrapartum outcome occurred in 25.3 % (95 % CI 18.8-32.5) of women undergoing IOL with Dinoprostone, compared to 7.4 % (95 % CI 3.9-11.7) of those with mechanical methods, while CS for NRFS was performed in 23.8 % (95 % CI 17.3-30.9) and 6.2 % (95 % CI 2.8-10.5) of the cases, respectively. Finally, in SGA fetuses, composite adverse intrapartum outcome complicated 8.4 % (95 % CI 4.6-13.0) of pregnancies induced with Dinoprostone, 18.6 % (95 % CI 13.1-25.2) of those with Misoprostol and 8.7 (95 % CI 2.5-17.5) of those undergoing mechanical IOL, while CS for NRF was performed in 8.4 % (95 % CI 4.6-13.0) of women induced with Dinoprostone, 18.6 % (95 % CI 13.1-25.2) of those with Misoprostol and 8.7 % (95 % CI 2.5-17.5) of those undergoing mechanical induction. Overall, the quality of the included studies was low and was downgraded due to considerable clinical and statistical heterogeneity.Conclusions: There is limited evidence on the optimal type of IOL in pregnancies with small fetuses. Mechanical methods seem to be associated with a lower occurrence of adverse intrapartum outcomes, but a direct comparison between different techniques could not be performed. [ABSTRACT FROM AUTHOR]

Objective: To compare the safety and clinical effectiveness of high-intensity focused ultrasound (HIFU) and uterine artery embolization (UAE) for retained placenta accreta.Study Design: A retrospective analysis was performed on women who underwent HIFU or UAE followed by hysteroscopic resection for retained placenta accreta from January 2015 to December 2019 at the Third Xiangya Hospital of Central South University.Results: A total of 63 and 31 patients who underwent HIFU and UAE followed by hysteroscopic resection, respectively, were analyzed. The baseline characteristics, including age, gravidity, parity, previous cesarean section rate, previous curettage rate, previous intrauterine adhesions rate, and delivery mode, were similar between the two groups. Vaginal bleeding was the major complaint in patients with retained placenta accreta. The number of hysteroscopy sessions, amount of intraoperative blood loss, and the length of hospital stays were also similar between the groups. No further hysterectomy was needed in either group.Conclusion: Both HIFU and UAE combined with hysteroscopic resection seem to be safe and effective procedures in cases of retained placenta accreta. [ABSTRACT FROM AUTHOR]

• The functioning of the placenta has far-reaching consequences. • The placenta fulfils functions of fetal organs as long as they are not fully functional. • The placenta provides specific information on organ function required for the development of AOPs. Despite the short lifespan of the human placenta, the proper formation and function of the organ is of crucial importance for fetal development. Placental dysfunction increases the risk of complications for mother and child during pregnancy and childbirth and beyond as it predisposes to fetal programming. The placenta is an upstream organ of the fetus. It performs the functions of fetal lungs, liver, intestines, kidneys and glands as long as these organs are not fully functional. Furthermore, it is the only human organ that is non-invasively available either after elective abortion or after birth. This is a crucial point given that the conceptual framework of Adverse Outcome Pathway (AOP) requires data on organ function. In vitro and ex vivo placental studies, combined with epidemiological and clinical data on pregnant women, newborns, and infants can uniquely cover all levels of information needed to develop new AOPs and complement existing AOPs related to reproductive toxicity and beyond. To stimulate further research in this area and to support researchers in future studies dealing with the development of AOPs related to the placenta, this review first gives a brief description of placental structure, placental development and relevant pregnancy diseases. The state of knowledge about the available placental models, their particularities and limitations are briefly discussed. Finally, the use of placental research for the development of AOPs is presented with an illustrative example. [ABSTRACT FROM AUTHOR]

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]

Every year, complications during pregnancy affect more than 26 million women. Some of those diseases are associated with significant morbidity and mortality, as is the case of preeclampsia, the main cause of maternal deaths globally. The ability to improve the delivery of drugs to the placenta upon administration to the mother may offer new opportunities in the treatment of diseases of pregnancy. The objective of this study was to develop megalin-targeting liposome nanocarriers for placental drug delivery. Megalin is a transmembrane protein involved in clathrin-mediated endocytic processes, and is expressed in the syncytiotrophoblast (SynT), an epithelial layer at maternal-fetal interface. Targeting megalin thus offers an opportunity for the liposomes to hitchhike into the SynT, thus enriching the concentration of any associated therapeutic cargo in the placental tissue. PEGylated (2 KDa) lipids were modified with gentamicin (GM), a substrate to megalin receptors as we have shown in earlier studies, and used to prepare placental-targeting liposomes. The ability of the targeting liposomes to enhance accumulation of a fluorescence probe was assessed in an in vivo placental model - timed-pregnant Balb/c mice at gestational day (GD) 18.5. The targeting liposomes containing 10 mol% GM-modified lipids increased the accumulation of the conjugated fluorescence probe in the placenta with a total accumulation of 2.8% of the initial dose, which corresponds to a 94 fold increase in accumulation compared to the free probe (p <.0001), and 2–4 fold accumulation compared to the non-targeting control liposomes (p <.0001), as measured by both tissue extraction assay and ex vivo imaging. Furthermore, confocal images of placental SynT cross-sections show a 3-fold increase of the targeting liposomes compared with the non-targeting liposomes. The rate and extent of uptake of a fluorescent probe encapsulated within targeting liposomes was also probed in an in vitro model of the human placental barrier (polarized BeWo monolayers) using flow cytometry. Targeting liposomes containing 5 mol% GM-modified lipids enhanced the uptake of the probe by 1.5 fold compared to the non-targeting control. An increase to 10 mol% of the modified lipid resulted in further enhancement in uptake, which was 2 fold greater compared to control. In a competition assay, inhibition of the megalin receptors resulted in a significant reduction in uptake of the fluorescence probe encapsulated in GM-modified liposomes compared to the uptake without free inhibitor (p <.0001), implicating the involvement of megalin receptor in the internalization of the liposomes. Taken together, these results demonstrate that megalin-targeted liposomes may offer an opportunity to enhance the delivery of therapeutics to the placenta for the treatment of diseases of pregnancy. Unlabelled Image • Megalin receptors expressed on the placenta are a valuable target for the targeted delivery of therapeutics to the placenta. • Gentamicin-modified liposomes significantly enhance placental uptake in pregnant Balb/c mice. • Gentamicin-modified liposomes significantly increase cellular uptake in an in vitro placental model (BeWo monolayer) • Gentamicin-modified liposomes show no significant accumulation in the fetal tissues of pregnant Balb/c mice. [ABSTRACT FROM AUTHOR]

• 25 plants were documented as remedies for retained placenta in Dinokana. • Hypoxis hemerocallidea and Drimia sanguinea had the highest frequency of citation. • Herbs were the most dominating plant-life form. • Roots were the most widely used plant part. Farmers and herders often interface ethno-veterinary knowledge and modern veterinary to treat their livestock. Viability of livestock production in local communities is continuously under the threat due to different diseases including retained placenta. The current study documented medicinal plants used to treat retained placenta and associated diseases in Dinokana communities, North West Province, South Africa. Ethnobotanical data was collected using semi-structured interviews. The collected data was presented as percentages and frequencies, use-value, frequency of citation and cultural importance index. In the study area, 25 plants from 18 families were indicated as remedies for the treatment of retained placenta in cattle. Hypoxis hemerocallidea, Peltophorum africanum, Drimia sanguinea and Elephantorrhiza elephantina were the most cited plants. The most dominating life forms were herbs (40%) and shrubs (36%). The plant parts commonly preferred in the preparation of remedies for retained placenta included the roots (36%) and leaves (21%) and whole plant (18%). Poultice (68%), maceration (24%) and decoction (8%) were the three methods of preparation that were described by the participants. Most (68%) of plants were administered topically. As indicated by the participants, at least 20% of the 25 medicinal plants had multiple indications (uses) either as single-plant or poly-plant remedies against diseases in cattle. Apart from retained placenta in cattle, these plant remedies were used for constipation, intestinal parasites, anaemia, pain and inflammation as well as diarrhoea. The study unravelled the rich indigenous knowledge on plants with ethno-veterinary value among Dinokana communities. Further studies are needed in order to determine biological activities and safety as well as the chemical profiles for these documented plants especially for those currently lacking scientific evidence on their efficacies. [ABSTRACT FROM AUTHOR]

Placentitis is an important cause of abortion, stillbirth, and neonatal death in horses. The diagnosis of placentitis is based on occurrence of clinical signs (premature mammary gland development and vulvar discharge) and ultrasonography of the caudal placental pole. However, early and subtle cases can be missed. In the last few years, several studies have provided objective means of diagnosing placentitis in mares with single or serial measurements of blood markers. Among the markers evaluated the steroids produced by the fetoplacental unit have been shown to change in association with placentitis. Mares with chronic placentitis have an increase in peripheral progestogens; however, mares acutely infected will display a reduction in peripheral concentrations of progestogens. Estradiol-17β (free- and conjugated form) concentrations are drastically reduced in plasma of mares with placentitis. Acute-phase proteins, particularly serum amyloid A, are increased in plasma of mares suffering from placentitis, and this increase is due to endometrial and chorioallantoic secretions, and minimally from the fetus. Alpha-fetoprotein, a protein expressed in the fetoplacental unit, was shown to be increased in plasma of mares suffering from placentitis. A plephora of microRNA have been identified in plasma and tissues of mares undergoing experimentally induced placentitis, but have not been tested in spontaneous cases. Unique proteomic signatures were found in the fetal fluids of mares undergoing experimentally induced ascending placentitis, making the fetal fluids potentially useful to diagnose placentitis in mares. However, currently the lack of use of transabdominal fetal fluid sampling prevents wide use of the fetal fluids as diagnostic techniques. This manuscript aimed to discuss recent discoveries regarding biomarkers for placentitis in mares. • Estradiol 17β in combination with progestogen appears to be the most useful hormones to be assessed in placentitis. • Serum amyloid A holds the potential to be a good prognostic marker in mares having no other confounding variables. • Alpha-fetoprotein appears to be a good prognostic marker for placentitis in mares and disease in foals. • Findings of experimental cases should also be confirmed in clinical trials involving field cases. • No marker should replace the value of an experiencing clinician examining the mare. However, the markers can be used to enhance the diagnostic capabilities. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence to support an association between placental inflammation and neurological sequelae of preterm infants. The goal of this study is to evaluate the relationship between placental pathology, post-natal Doppler cerebral resistive indices (RI's), and intraventricular hemorrhage (IVH) in premature infants.Methods: In a retrospective cohort study, preterm infants born between 23 0/7 and 32 6/7 weeks' gestation at Parkland Hospital were examined with placental pathology and serial ultrasound Doppler to evaluate for the primary outcome of IVH and death.Results: A total of 255 infants were included, and 166 (65%) had at least one significant placental pathology, most commonly chorioamnionitis. Infants with placental pathologies were significantly more likely to have mothers with clinical chorioamnionitis and to have lower gestational ages. There was no observed association between placental pathology and IVH or death. Secondary analysis demonstrated that resistive indices obtained from the first and second head ultrasounds were not different in infants with IVH.Conclusion: In this study, we observed a high rate of placental pathologies but no alterations in cerebral indices on ultrasound, or differences in rates of IVH or death. Additional studies are necessary to delineate the relationship between placental pathology, white matter brain injury, and outcomes. [ABSTRACT FROM AUTHOR]

What are the clinical characteristics of pregnancies complicated by fetal growth restriction (FGR) and preeclampsia in patients who have undergone IVF, and what is the correlation between these complications and histopathological placental findings in such pregnancies. A retrospective cohort of patients who had delivered their babies at our institution who had been diagnosed with preeclampsia, whose babies had been diagnosed with FGR, or both. Deliveries in which the placenta was sent for histopathological examination were included. Computerized files and pathological reports were reviewed, and maternal, obstetric, neonatal outcomes and placental histopathological reports were compared between pregnancies conceived by IVF and controls. Placental lesions were classified according to the Amsterdam criteria. Between December 2008 and December 2018, the placentas of 1114 singleton babies who had received a diagnosis of FGR, whose mothers had received a diagnosis of preeclampisa, or both, were examined. A total of 105 patients conceived with IVF and 1009 were conceived spontaneously. The IVF group was older, of lower parity and had a higher rate of diabetes and chronic hypertension. Deliveries occurred at an earlier gestational age, although birth weight was not significantly different between the groups. The rate of neonatal adverse composite outcome among IVF deliveries was significantly lower (59.0% versus 76.7%; P < 0.001). On placental examination, placental weight, maternal and fetal vascular malperfusion lesions were similar between the groups, whereas villitis of unknown etiology was significantly more common among the IVF group (16.2% versus 8.3%; P = 0.007). Neonatal outcome is relatively favourable in IVF patients with placental-related diseases. Placental chronic villitis is more common in IVF patients, pointing to an additive immunological cause. [ABSTRACT FROM AUTHOR]