Placental Pathologic Findings Research Articles

Maternal COVID-19 exposure and placental characteristics.

The impact of COVID-19 on the placenta is poorly described, particularly among minority women. This is a retrospective case-control study. Micro- and macroscopic placental pathologic findings were compared for 15 COVID-19 positive and 36 negative mothers. Cases and controls were frequency matched on gestational age, race, maternal comorbidities, and delivery type. Data from the electronic medical record were supplemented with independent review of microscopic slides. Placentas from cases and controls were similar except the median distance from the site of the cord insertion to the nearest disk margin was statistically significantly shorter among placentas from COVID-19 positive cases (3.5 versus 6.0 cm, p = 0.006). Case status was not associated with an increased risk of placental pathologies. There are few pathologic differences between placentas of COVID-19 positive and negative mothers. Additional studies are needed to investigate the role of timing of infection.

Placental pathology and neonatal morbidity: exploring the impact of gestational age at birth

AimTo evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome.MethodsThis prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score < 7, umbilical cord artery pH < 7.0, admission to the neonatal intensive care unit or intrauterine death. A composite adverse outcome included one or more adverse outcomes. The associations between placental pathology, adverse neonatal outcomes, maternal and pregnancy characteristics were evaluated by logistic regression analysis.ResultsLate-term and post-term births exhibited significantly higher rates of histologic chorioamnionitis (HCA), fetal inflammatory response, clinical chorioamnionitis (CCA) and transfer to neonatal intensive care unit (NICU) compared to early-term and term births. HCA and maternal smoking in pregnancy were associated with adverse outcomes in an adjusted analysis. Nulliparity, CCA, emergency section and increasing GA were all significantly associated with HCA.ConclusionsHCA was more prevalent in late and post-term births and was the only factor, along with maternal smoking, that was associated with adverse neonatal outcomes. Since nulliparity, CCA and GA beyond term are associated with HCA, this should alert the clinician and elicit continuous intrapartum monitoring for timely intervention.

Covid-19 vaccination in pregnancy and placental pathology

Objective: To describe and determine the association between Covid-19 vaccination in pregnancy and placental pathology. Methods: Conducted in a tertiary hospital in Medan, Indonesia, from April 30th 2022 to June 30th 2022, this single-center cross-sectional study involved Covid-19 vaccinated and unvaccinated women with singleton full-term pregnancies delivering live fetuses via cesarean section. Maternal characteristics, placental pathologies, and the placental index were documented at enrollment. The association between Covid-19 vaccination status and placental pathology was assessed. Results: The study enrolled 200 pregnant women, including 110 vaccinated women and 90 unvaccinated women. No significant differences were observed in birthweight (P=0.48), placental index (P=0.48), and placental pathology findings [intervillous bleeding (P=0.20), increased syncytial knots (P=0.83), chorangiosis (P=0.13), villous stromal edema (P=0.13), vascular dilation and congestion (P=0.13), and vascular wall thrombus (P=0.71)] between the vaccinated and unvaccinated groups. Conclusions: This study revealed no statistically significant association between Covid-19 vaccination and placental pathology. The findings support the safety of Covid-19 vaccination during pregnancy, in regards to changes of the placental pathology.

Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence

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 one or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. To determine how quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent/reversed umbilical artery Doppler indices, hypertensive disorders of pregnancy, and the two conditions combined among subjects with disease severity warranting early preterm delivery. We hypothesize that trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulate 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 four groups: [1] Severe fetal growth restriction with absent/reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, [2] Severe fetal growth restriction with absent/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. 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 with linear regression. Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi, 95% CI: [-467, -98], p<0.01), smaller stem villous area (-4.3 mm2, 95% CI: [-7.3, -1.2], p<0.01), and fewer stem villous vessels (-4967 stem villous vessels, 95% CI [-8501, -1433], p<0.01), with no difference in total vascular area. In contrast, placental abnormalities in severe growth restriction were limited to terminal villi, with global decreases in number of villi (-873 terminal villi, 95% CI: [-1501, -246], p<0.01), villous area (-1.5 mm2, 95% CI: [-2.7, -0.4], p<0.01), number of blood vessels (-5165 terminal villous vessels, 95% CI: [-8201, -2128], p<0.01), and vascular area (-0.6 mm2, 95% CI: [-1.1, -0.1], p=0.02). 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/reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions with the combination of growth restriction and hypertension, suggesting that distinct pathophysiologic pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to result in more severe pathologic consequences. Delineating mechanisms underlying the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Etiology of stillbirth in a tertiary care center: a retrospective cohort study assessing ultrasound, laboratory, and pathology investigations

Background Canadian stillbirth data are limited, and a significant proportion of pregnancies resulting in stillbirth have no attributable cause. The objective of this study was to characterize stillbirth case investigations and management at a tertiary care hospital in Ontario, Canada. Methods This was a retrospective chart review study of all cases of singleton stillbirth at The Ottawa Hospital between 1 January 2012 and 31 December 2017. Terminations and multiples stillbirths were excluded. Chart reviews were conducted to extract maternal sociodemographic, obstetrical, and fetal characteristics, including results from antenatal ultrasounds, autopsy, placenta pathology, and laboratory investigations. Results A total of 155 eligible cases of stillbirth were identified, resulting in a 6-year stillbirth rate of 4.2 per 1000 total births. The median maternal age was 31.0 years (IQR: 29.0, 35.0) and the median gestational age at delivery was 28 weeks (IQR: 24, 35). A total of 9 (5.8%) pregnant individuals had a history of previous stillbirth. Of the 155 stillbirths, 35% underwent the full suite of post-loss laboratory, placental, and fetal autopsy investigations. 63.2% of cases had post-loss laboratory investigations completed. 76% and 71% of cases had fetal autopsy and placenta pathology evaluations completed, respectively. Antenatal characteristics associated with stillbirth included fetal anomalies/genetic markers (27.1%), umbilical cord and placental anomalies (24.5%), fetal growth abnormalities (27.7%), cervical/uterine abnormalities (11.6%), and amniotic fluid abnormalities (25.1%). The most common autopsy findings included evidence of infection (22.7%), fetal anomalies (12.6%), and fetal hypoxia (10%). The most common placental pathology findings included features of placental insufficiency (21.8%), retroplacental abnormalities (16.3%), and umbilical cord accident/infarct (15.4%). Conclusions Our findings demonstrate that as many as two-thirds of singleton stillbirth cases at our center did not receive the post-perinatal loss investigations recommended by clinical practice guidelines. More thorough collection of post-stillbirth data at all levels (institutional, provincial, national) is warranted to improve our understanding of stillbirth epidemiology, etiology, and management in Canada.

Gross and Histologic Placental Abnormalities Associated With Neonatal Hypoxic-Ischemic Encephalopathy.

To elucidate particular placental pathology findings that are associated with hypoxic ischemic encephalopathy (HIE) and determine which patterns are associated with adverse fetal/neonatal outcomes. Multi-institutional retrospective case-control study of newborns with HIE (2002-2022) and controls. Four perinatal pathologists performed gross and histologic evaluation of placentas of cases and controls. A total of 265 placentas of neonates with HIE and 122 controls were examined. Infants with HIE were more likely to have anatomic umbilical cord abnormalities (19.7% vs 7.4%, P = .003), fetal inflammatory response in the setting of amniotic fluid infection (27.7% vs 13.9%, P = .004), and fetal vascular malperfusion (30.6% vs 9.0%, P = <.001) versus controls. Fetal vascular malperfusion with maternal vascular malperfusion was more common in those who died of disease (P = .01). Placental pathology examination of neonates with HIE may improve our understanding of this disorder and its adverse outcomes.

Placental Histologic Abnormalities and 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy

Objective: We aimed to examine the association between placental abnormalities and neurodevelopmental outcomes in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) that underwent therapeutic hypothermia. We hypothesized that subjects with acute placental abnormalities would have reduced risk of death or neurodevelopmental impairment (NDI) at 2 years of age after undergoing therapeutic hypothermia compared to subjects without acute placental changes. Study Design: Among 500 subjects born at ≥36 weeks gestation with moderate or severe HIE enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, a placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute only, chronic only, or both acute and chronic histologic abnormalities. We calculated adjusted relative risks (aRRs) for associations between placental pathologic abnormalities and death or NDI at age 2 years, adjusting for HIE severity, treatment assignment, and site. Result: 321/500 subjects (64%) had available placental pathology reports. Placental abnormalities were characterized as acute only (20%), chronic only (21%), both acute and chronic (43%), and none (15%). The risk of death or NDI was not statistically different between subjects with and without an acute placental abnormality (46 vs. 53%, aRR 1.1, 95% confidence interval (CI): 0.9, 1.4). Subjects with two or more chronic lesions were more likely to have an adverse outcome than subjects with no chronic abnormalities, though this did not reach statistical significance (55 vs. 45%, aRR 1.24, 95% CI: 0.99, 1.56). Conclusion: Placental pathologic findings were not independently associated with risk of death or NDI in subjects with HIE. The relationship between multiple chronic placental lesions and HIE outcomes deserves further study.

Placental Pathology Findings in Unexplained Pregnancy Losses.

There are approximately 5 million pregnancies per year in the USA, with 1 million ending in miscarriage (a loss occurring prior to 20weeks of gestation) and over 20,000 ending in stillbirth at or beyond 20weeks of gestation. As many as 50% of these losses are unexplained. Our objective was to evaluate the effect of expanding the placental pathology diagnostic categories to include the explicit categories of (1) dysmorphic chorionic villi and (2) small placenta in examining previously unexplained losses. Using a clinical database of 1256 previously unexplained losses at 6-43weeks of gestation, the most prevalent abnormality associated with each loss was determined through examination of its placental pathology slides. Of 1256 cases analyzed from 922 patients, there were 878 (69.9%) miscarriages and 378 (30.1%) antepartum stillbirths. We determined the pathologic diagnoses for 1150/1256 (91.6%) of the entire series, 777/878 (88.5%) of the miscarriages (< 20weeks' gestation), and 373/378 (98.7%) of the stillbirths (≥ 20weeks' gestation). The most common pathologic feature observed in unexplained miscarriages was dysmorphic chorionic villi (757 cases; 86.2%), a marker associated with genetic abnormalities. The most common pathologic feature observed in unexplained stillbirths was a small placenta (128 cases; 33.9%). Our classification system reinforced the utility of placental examination for elucidating potential mechanisms behind pregnancy loss. The improved rate of diagnosis appeared to be the result of filling a gap in previous pregnancy loss classification systems via inclusion of the categories of dysmorphic chorionic villi and small placenta.

Prenatal Brain Maturation is Delayed in Neonates with Congenital Diaphragmatic Hernia

To assess brain development in fetuses with congenital diaphragmatic hernia (CDH) using a fetal Total Maturation Score (fTMS). This is a retrospective cohort study using data from a single-center, clinical registry. Neonates with an antenatal diagnosis of CDH between 2014 - 2020 and prenatal brain magnetic resonance imaging (n = 48) were included. We compared our study sample with historical healthy controls (n = 48). The relationship between fTMS and gestational age, as well as the association between fTMS and key prenatal variables and placental pathologic findings, were evaluated. Compared with healthy controls, neonates with CDH had a significant delay in fTMS (p-value <0.001). Within the CDH cohort, there was no significant difference in fTMS based on CDH severity, intrathoracic liver position, right versus left CDH, sex, presence of abnormal echocardiogram findings, treatment with extracorporeal membrane oxygenation, or in-hospital mortality. Placentas of neonates with CDH had a high proportion of fetal vascular malperfusion (56%) and chronic inflammation (67%), and relatively large placentas had a protective effect on prenatal brain maturation (p-value = 0.025). Prenatal brain maturation in neonates with CDH is delayed. Placental pathology may influence fetal brain development. The etiology and clinical impact of prenatal brain immaturity in neonates with CDH warrant further investigation.

Placental pathology and clinical findings in pregnant women infected with SARS-CoV-2

Placental pathology and clinical findings in pregnant women infected with SARS-CoV-2

Does maternal vitamin D status influence placental weight or vascular and inflammatory pathology? Secondary analysis from the Kellogg Pregnancy Study

IntroductionPositive effects of vitamin D (vitD) supplementation on comorbidities of pregnancy (COP) have been explored; however, few studies have elucidated the pathophysiology behind the development of these COP and the potential relationship with derangements in placental development and morphology. Additionally, it is known that placentas weighing 10th-90th % for gestational age are associated with better outcomes. Therefore, the objective of this study was to assess the impact of resulting circulating serum 25(OH)D concentrations associated with intake of high or low doses of supplementary vitD on placental development and morphology in women who participated in a randomized double blind, placebo-controlled trial of vitD supplementation. We hypothesized that if maternal serum 25(OH)D concentration (vitD status marker) is insufficient/deficient, then placental weight and % for gestational age (GA) will be smaller and will correlate with increased vascular and inflammatory placental pathologic findings. MethodsThe findings of the present study are a secondary analysis of data generated from a previously reported randomized controlled trial (RCT), the Kellogg Vitamin D Pregnancy Study. Pregnant women (n = 297) in this RCT (January 2013 - April 2018) were randomly assigned to 400 IU vs. 4400 IU vitD/day (10–14 weeks’ gestational age) and followed to delivery. 132 placentas were analyzed by pathologists blinded to treatment, and the 2016 Amsterdam Consensus Criteria were used to categorize grouping/grading of placental pathology and weight. Total [25(OH)D] was measured using radioimmunoassay (ng/mL). Chi-square and Student’s t-test were used to show the difference in maternal characteristics by treatment group and by placental weight. Chi-square analysis was used to determine differences between the percent pathology findings by treatment group. Students t-test was used to determine the differences in vitD status and the frequency of placental lesions. Association between [25(OH)D] area under the curve (AUC) and placental morphology were determined in a regression model that included maternal BMI ≥ 30 kg/m2, race/ethnicity, and vitD treatment group allocation. Data were analyzed using SAS v9.4 (Cary, NC) and statistical significance was indicated by p < 0.05. ResultsThe percent pathology findings by treatment group were not significantly different for each of the placental pathology categories as defined by the 2016 Amsterdam Consensus Criteria including placental weight. However, when using 25(OH)D as a biomarker for vitD status, linear regression model showed maternal serum [25(OH)D] AUC was significantly associated with greater placental weight (p = 0.023). Logistic regression models showed mothers with BMI ≥ 30 kg/m2 had larger placental weight (p = 0.046), and Hispanic and white/Caucasian mothers had greater placental weights than Black American mothers (p = 0.025). When placentas ≥ 90th % for GA, n = 7, were removed from the placental pool, Pearson correlation still showed a positive association between maternal serum 25(OH)D AUC and placental weight (p = 0.011). In a second linear regression model of placentas ≥ 90th % for GA (n = 7) vs. placentas < 90th % (n = 108), maternal serum 25(OH)D AUC was significantly greater in those placentas ≥ 90th % (p = 0.03); however, this was not associated with increased perinatal mortality. Conclusion findingssuggest increasing maternal serum [25(OH)D] via vitamin D supplementation during pregnancy did not adversely affect placental morphology; trends showed those in the treatment group had fewer placental lesions. Placental weight was found to be significantly associated with [25(OH)D] AUC, which represents maternal vitamin D status over the course of pregnancy; 7 placentas ≥ 90th % for GA were not associated with perinatal mortality.

Placental pathology findings in perinatal deaths from 28 weeks gestation in Aotearoa New Zealand

IntroductionWomen of South Asian ethnicity are overrepresented in adverse pregnancy outcome across high-income countries, including those related to placental dysfunction. It has been hypothesised that placental aging occurs at earlier gestation in South Asian pregnancies. We aimed to identify differences in placental pathology among perinatal deaths ≥28 weeks gestation, between South Asian, Māori and New Zealand (NZ) European women in Aotearoa NZ, with a focus on women of South Asian ethnicity. MethodsPlacental pathology reports and clinical data from perinatal deaths between 2008 and 2017 were provided by the NZ Perinatal and Maternal Mortality Review Committee, blinded, and analysed by an experienced perinatal pathologist using the Amsterdam Placental Workshop Group Consensus Statement criteria. Results790 of 1161 placental pathology reports, 346 preterm (28+0 to 36+6 weeks) and 444 term (≥37+0 weeks) deaths, met the inclusion criteria. Among preterm deaths, South Asian women had higher rates of maternal vascular malperfusion compared with Māori (aOR 4.16, 95%CI 1.55–11.15) and NZ European (aOR 2.60, 95%CI 1.10–6.16). Among term deaths, South Asian women had higher rates of abnormal villous morphology compared with Māori (aOR 2.19, 95%CI 1.04–4.62) and NZ European (aOR 2.12, 95%CI 1.14–3.94), mostly due to increased rates of chorangiosis (36.7%, compared to 23.3% and 21.7%, respectively). DiscussionDifferences in placental pathology by ethnicity were observed among preterm and term perinatal deaths. While we suspect differing underlying causal pathways, these deaths may be associated with maternal diabetic and red blood cell disorders among South Asian women, leading to a hypoxic state in-utero.

Leveraging the placenta to advance neonatal care.

The impact of placental dysfunction and placental injury on the fetus and newborn infant has become a topic of growing interest in neonatal disease research. However, the use of placental pathology in directing or influencing neonatal clinical management continues to be limited for a wide range of reasons, some of which are historical and thus easily overcome today. In this review, we summarize the most recent literature linking placental function to neonatal outcomes, focusing on clinical placental pathology findings and the most common neonatal diagnoses that have been associated with placental dysfunction. We discuss how recent technological advances in neonatal and perinatal medicine may allow us to make a paradigm shift, in which valuable information provided by the placenta could be used to guide neonatal management more effectively, and to ultimately enhance neonatal care in order to improve our patient outcomes. We propose new avenues of clinical management in which the placenta could serve as a diagnostic tool toward more personalized neonatal intensive care unit management.

Placental pathology findings amongst extremely preterm perinatal deaths in Aotearoa New Zealand

IntroductionWomen of South Asian ethnicity are overrepresented in adverse pregnancy outcomes across high-income countries, including placental dysfunction and antepartum haemorrhage. As the burden of mortality is highest for extremely preterm infants, we aimed to identify any differences in placental pathology among perinatal deaths from 20+0 to 27+6 weeks gestation between South Asian, Māori and New Zealand (NZ) European women in Aotearoa NZ, with a focus on women of South Asian ethnicity. MethodsPlacental pathology reports and clinical data from perinatal deaths between 2008 and 2017 were provided by the NZ Perinatal and Maternal Mortality Review Committee, blinded and analysed by an experienced perinatal pathologist using the Amsterdam Placental Workshop Group Consensus Statement criteria. South Asian ethnicity was classified as Indian, Fijian Indian, South African Indian, Sri Lankan, Pakistani and Bangladeshi. Results886 of 1571 placental pathology reports met the inclusion criteria. Women of South Asian ethnicity were significantly more likely to show features of histologic chorioamnionitis (aOR 1.87, 95%CI 1.19–2.94) and chorionic vasculitis (aOR 1.92, 95%CI 1.13–3.29), than NZ European and Māori women respectively. 13 of 15 (87%) of South Asian mothers with a diabetic disorder were identified with chorioamnionitis, compared to 1 in 5 (20%) of Māori and 5 in 12 (41%) of NZ European women. Cord hyper-coiling was also more common among South Asian pregnancies, compared to NZ European (aOR 1.98, 95%CI 1.10–3.56). DiscussionDifferences in placental pathology by ethnicity were observed among extremely preterm perinatal deaths. Underlying metabolic disorders and an associated pro-inflammatory environment may play an important role in the causal pathway leading to these deaths in women of South Asian ethnicity.

Analysis of placental pathology after COVID-19 by timing and severity of infection

COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Evaluation of placental pathologies in cases of placenta previa

Objective: The primary aim of our study was to evaluate the underlying placental pathologies of placenta previa (PP). &#x0D; Materials and Methods: Over two years data of patients diagnosed to be PP in a tertiary center were obtained retrospectively. Routinely, the placentas of patients diagnosed to be PP were sent for pathological examination. Clinicodemographic data of the patients were recorded. The placental pathological findings were classified and evaluated in 5 main groups: maternal vascular lesions, fetal vascular lesions, inflammatory situations, umbilical cord findings, and normal. Additionally, complete blood count results at admission time for hospitalization and the outcomes of the neonates were recorded.&#x0D; Results: Thirty-two patients diagnosed to be PP were included in the study. The median age was 34 (22-42), and the median gravidity number was 3 (1-6). Maternal vascular lesions were observed in nearly half of the PP patients as a pathological finding (43.75 %). Inflammation was observed in 10 patients (31.25 %), umbilical cord findings in 8 patients (25.0 %), and fetal vascular lesions in 2 patients (6.25 %), respectively. 3 patients were reported to have normal placentas. In addition, the median neutrophile, neutrophile lymphocyte ratio, and white blood count were found to be high at admission time for hospitalization&#x0D; Conclusion: Maternal vascular lesions and inflammation were the most common detected placental pathological reports in PP patients. However, studies including the placentas of uncomplicated pregnancies will shed light on the literature to distinguish the pathological condition from the physiological condition.

The Multifaceted Clinical Characteristics of Congenital Cytomegalovirus Infection: From Pregnancy to Long-Term Outcomes.

The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6-40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

Pathological Examination of the Placenta in COVID-19-Positive Mothers: A Short Communication.

It was declared that COVID-19 might be more severe in symptomatic pregnant patients. This study was conducted to examine the pathological indices of the placenta in pregnant women who were diagnosed with COVID-19. A total of 20 COVID-19-positive mothers were enrolled in this study. Detailed placental pathology findings were compared between subjects based on the history of abortion or occurrence of preterm delivery, hypertension, and diabetes. Intervillositis was the most frequent abnormality of the placenta. There was also a significant association between abortion history and maternal vascular malperfusion (MVM; P=0.02). The placental abnormalities were found to be increased in women with COVID-19, regardless of maternal comorbidities. Further studies are needed to compare the placental pathology between COVID-19-positive women and healthy women.

SARS-CoV-2 placentitis, stillbirth, and maternal COVID-19 vaccination: clinical–pathologic correlations

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 findings present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition which typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis. These three pathological lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect greater than 75% of the placenta, effectively rendering the placenta 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 immunological 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 pathological aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis and perinatal death.

Histopathologic evaluation of dichorionic twin placentas in unassisted and in vitro fertilized pregnancies affected by preeclampsia

Objective Pregnancies achieved with assisted reproductive technology have an increased risk of multiple gestations, preeclampsia, and placental morphologic abnormalities. Inflammatory processes affect dichorionic twin pregnancies disproportionately more than singleton gestations and have been associated with adverse pregnancy outcomes, such as fetal growth restriction and preeclampsia. Our objective is to investigate the placental morphology of dichorionic twin pregnancies complicated by preeclampsia conceived with in vitro fertilization (IVF) versus unassisted. Methods This is a retrospective analysis of placentas from dichorionic twin pregnancies affected by preeclampsia conceived with IVF versus without assistance from 2010 to 2016 at a tertiary care university hospital. Placental pathology findings were analyzed both independently and in aggregate stratified into composite outcome scores using a modified placental synoptic framework. Individual placental abnormalities were grouped into composite categories based on the site of origin: anatomic placental abnormalities; maternal vascular malperfusion; placental villous maldevelopment; fetal vascular malperfusion; chronic utero-placental separation; maternal-fetal interface disturbance; inflammation of infectious etiology; and inflammation of idiopathic etiology. Placental histopathological statistical analysis was performed using Fisher’s exact test. Demographic variables and pregnancy outcomes were compared between groups using the Student’s t test or Mann-Whitney U test, where appropriate. p < .05 defined statistical significance. Results Of 117 dichorionic twin pregnancies, 60 resulted from IVF (Group A) and 57 were conceived without assistance (Group B). Patients in Group A were older (36 [29–37] vs. 33 [32–38] respectively; p = .042) and less parous (18.3% vs. 38.6% percent parous in Group A and Group B, respectively p = .009) than Group B, respectively. No differences were found between groups regarding mode of delivery, gestational age at delivery, placental weight/birthweight, fetal growth restriction, and discordance of fetal growth. There were significantly more inflammatory changes of unknown etiology and composite inflammatory abnormalities in Group A versus Group B (26.7% vs. 10.5%, p = .02). The cumulative number of inflammatory abnormalities per patient had a significantly different distribution among groups (p = .005), and Composite Chronic Inflammation and Infection were found to be significantly more abundant in Group A versus Group B (p = .02). The distribution of placental composite anatomic placental abnormalities, maternal vascular malperfusion, placental villous maldevelopment, fetal vascular malperfusion, chronic utero-placental separation, or maternal-fetal interface disturbance was not statistically different between groups. The distribution of placental abnormalities was not different between groups for any individually analyzed pathological condition. Due to the relatively small sample size, adjustment for potential confounders was not performed. Conclusion Dichorionic twin pregnancies affected by preeclampsia are associated with more placental inflammatory abnormalities if conceived with IVF versus unassisted. Further research is needed to ascertain the underlying mechanisms of these observed differences.