Placental mesenchymal disease masquerading as molar pregnancy with a favourable maternal and fetal outcome.

Placental mesenchymal dysplasia (PMD) is an exceptionally rare placental anomaly characterised by placentomegaly and grape-like vesicles resembling partial mole on ultrasonography, yet it can coexist with a viable fetus. We present the case of a primigravida who presented at 22 weeks gestation with a suspected partial mole but with a normally growing fetus. The differential diagnoses considered included placental mesenchymal disease, partial mole and twin pregnancy with molar pregnancy. With normal beta HCG levels and prenatal invasive testing reports, a probable diagnosis of PMD was made, and after thorough counselling, the decision was made to continue the pregnancy. The pregnancy progressed until 37 weeks, culminating in the uneventful delivery of a 2.4 kg healthy male infant. Histopathology confirmed PMD. Early recognition and management of PMD pose significant challenges, given its rarity. Prenatal identification of PMD during both early and late gestation could avert unnecessary termination of pregnancy.

An Update on COVID-19-Associated Placental Pathologies.

COVID-19 pregnancies are associated with increased rates of premature delivery and stillbirths. It is still a matter of debate whether there is a COVID-19-associated pattern of placenta pathology. We updated our previously published results on a systematic literature review and meta-analysis of COVID-19 pregnancies. In total, 38 reports on 3677 placentas were evaluated regarding histopathological changes. Maternal vascular malperfusion (32%), fetal vascular malperfusion (19%), acute and chronic inflammation (20% and 22%) were frequent pathologies. In non-COVID-19 pregnancies, placentas show similar histologic patterns and mainly similar frequencies of manifestation. It has to be taken into account that there might be an observation bias, because some findings are diagnosed as a "pathology" that might have been classified as minor or unspecific findings in non-COVID-19 placentas. COVID-19 placentitis occurs in 1-2% of cases at the most. In conclusion, this updated meta-analysis indicates that COVID-19 infection during pregnancy does not result in an increased rate of a specific placenta pathology and COVID-19 placentitis is rare.

Massive perivillous fibrin deposition: Diagnosis, obstetrical features, and treatment.

MPVFD (Massive perivillous fibrin deposition) is placental lesion characterized by extensive massive deposits of fibrin in the intervillous space, extending over at least 25 % of the placental volume. Currently, this pathology can only be detected through histopathological examination of the placenta after a pregnancy has ended. The underlying mechanisms are poorly studied, there is no biomarker available for the diagnosis of MPVFD and treatment protocols are experimental and still lacking. The objective of this study is to systematically review the literature on the associated clinicopathologic features, treatment, and prognosis of MPVFD. We ended up with 17 studies, of these 12 studies were considered relevant for this article and included in the final analysis. All studies reporting MPVFD are retrospective. MPVFD is associated with recurrent miscarriage, intra uterine fetal death (IUFD), intra uterine growth restriction (IUGR) and preterm delivery. The prevalence in pregnancies with a delivery after 22 weeks of gestation was at 1.1 % and even higher to 2.7 % in recurrent early miscarriages. The reported risk of fetal death in MPVFD ranges mainly from 15 to 80 %. Preterm delivery is spontaneous in 50 to 70 % of cases and induced by of a severe intrauterine growth restriction (IUGR) in 30 to 50 % of cases depending on the study. Its causes and treatment are still poorly understood, although several avenues have been explored. This review summarizes current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology, and potential prophylaxis against recurrence in this chronic inflammatory placental syndrome.

A novel technique to estimate intravillous fetal vasculature on routine placenta histologic sections.

Placental histopathologic lesions are dichotomized into "present" or "absent" and have limited inter-rater reliability. Continuous metrics are needed to characterize placental health and function. Tissue sections (N = 64) of human placenta were stained with CD34 antibody and hematoxylin. Proportion of the villous space occupied by fetal vascular endothelium (%FVE; pixels positive for CD34/total pixels) was evaluated for effect sizes associated with pregnancy outcomes, smoking status, and subtypes of lesions (n = 30). Time to fixation>60 min significantly increased the quantification. Large effect sizes were found between %FVE and both preterm birth and intrauterine growth restriction. These results demonstrate proof-of-concept for this vascular estimation.

Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease.

Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.

Outcome-Based Risk Stratification Model for the Diagnosis of Placental Maternal Vascular Malperfusion.

The Amsterdam Consensus Statement introduced the term maternal vascular malperfusion (MVM) to group a constellation of findings associated with impaired maternal-placental circulation. In isolation, these findings are relatively common in placentas from normal gestations, and there is uncertainty on how many, and which, are required. We aimed to determine the criteria essential for MVM diagnosis in correlation with obstetrical outcomes. A total of 200 placentas (100 with a reported diagnosis of MVM and 100 controls matched by maternal age and gravida-para-abortus status) were reviewed to document MVM features. Obstetrical outcomes in the current pregnancy were recorded including hypertension, pre-eclampsia with or without severe features, gestational diabetes, prematurity, fetal growth restriction, and intrauterine fetal demise. On univariate logistic regression analysis, adverse outcome was associated with low placental weight (LPW, <10% percentile for gestational age), accelerated villous maturation (AVM), decidual arteriopathy (DA), infarcts (presence and volume), distal villous hypoplasia, and excess multinucleated trophoblast in basal plate ≥2 mm (all P < .01) but not with retroplacental hemorrhage. In a multivariable model DA, infarcts and AVM were significantly associated with adverse outcomes, whereas LPW showed a trend toward significance. A receiver-operating characteristic curve including these 4 parameters showed good predictive ability (area under the curve [AUC], 0.8256). Based on the probability of an adverse outcome, we recommend consistent reporting of DA, AVM, infarcts, and LPW, summarizing them as "diagnostic of MVM" (DA or AVM plus any other feature, yielding a probability of 65%-97% for adverse obstetrical outcomes) or "suggestive of MVM" (if only 1 feature is present, or only 2 features are infarcts plus LPW, yielding a probability of up to 52%). Other features such as distal villous hypoplasia, excess (≥2 mm) multinucleated trophoblast, and retroplacental hemorrhage can also be reported, and their role in MVM diagnosis should be further studied.

Fetal survival in pregnancy complicated by massive subchorionic thrombohaematoma.

This case involves a pregnant patient in her late 20s whose pregnancy was complicated by placentamegaly and early-onset, severe fetal growth restriction (FGR). Investigations ruled out genetic and infectious aetiologies. The pregnancy eventually was further complicated by abnormal umbilical artery blood flow. Shared decision-making with the patient and obstetrical team led to delivery by caesarean section at 28 weeks and 4 days. The baby was admitted to the neonatal intensive care unit but, overall, did well. Placental pathology revealed a massive subchorionic thrombohaematoma (MST). This case highlights the importance of early detection, evaluation and management of pregnancies complicated by severe FGR as well as the significance of shared decision-making with patients. We aim to increase the awareness of MST in the differential diagnosis of placentamegaly, as this finding in combination with early and severe FGR has been shown to be a poor prognostic factor for the fetus.

Maternal and fetal outcomes of intraplacental choriocarcinoma complicated by fetomaternal hemorrhage: a systematic review.

INTRODUCTION: Intraplacental choriocarcinoma is a gestational trophoblastic neoplasia located within the placenta. Due to the usual silent presentation, more than half of the cases are diagnosed incidentally. It has been demonstrated that this pathology is linked to feto-maternal hemorrhage (FMH), stillbirth, and intrauterine growth restriction. The aim of our review was to establish if there are recurrent signs that might lead to an early diagnosis and better management in cases complicated by FMH. MATERIALS AND METHODS: We performed a systematic review of the literature from 2000 up to March 2023. The adopted research strategy included the following terms: (gestational choriocarcinoma obstetrics outcome) AND (intraplacental choriocarcinoma) AND (gestational choriocarcinoma). The MEDLINE (PubMed), Google Scholar, and Scopus databases were searched. RESULTS: The research strategy identified 19 cases of FMH coexisting with intraplacental choriocarcinoma (IC), as described in 17 studies. The perinatal mortality rate was 36.8%. In eight cases, histological diagnosis of IC was made post-delivery. Metastatic lesions were found in 75% (6/8) of described cases. One case of maternal death has been described. Chemotherapy was necessary in seven cases. Sporadical prenatal ultrasound signs were described. DISCUSSION: The diagnosis of IC is usually delayed, mostly due to aspecific symptoms and signs. Histological analysis of the placenta, when not routinely performed, should be performed when warning symptoms are encountered. The maternal prognosis was good, with a mortality rate of 5.5%. A fertility-sparing approach is always possible even in the presence of metastasis. Chemotherapy seems to be useful in cases of maternal and neonatal metastasis.

Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction.

Fetal growth restriction (FGR) leading to low birth weight (LBW) is a major cause of neonatal morbidity and mortality worldwide. Normal placental development involves a series of highly regulated processes involving a multitude of hormones, transcription factors, and cell lineages. Failure to achieve this leads to placental dysfunction and related placental diseases such as pre-clampsia and FGR. Early recognition of at-risk pregnancies is important because careful maternal and fetal surveillance can potentially prevent adverse maternal and perinatal outcomes by judicious pregnancy surveillance and careful timing of birth. Given the association between a variety of circulating maternal biomarkers, adverse pregnancy, and perinatal outcomes, screening tests based on these biomarkers, incorporating maternal characteristics, fetal biophysical or circulatory variables have been developed. However, their clinical utility has yet to be proven. Of the current biomarkers, placental growth factor and soluble fms-like tyrosine kinase 1 appear to have the most promise for placental dysfunction and predictive utility for FGR.

Misdiagnosis of placental mesenchymal dysplasia as pregnancy with hydatidiform mole: A case report and literature review.

RATIONALE: Placental mesenchymal dysplasia (PMD) is a rare placental disease frequently associated with severe maternal and/or fetal complications. Its sonographic appearance is very similar to that of a hydatidiform mole. Hence, PMD is easily misdiagnosed as a hydatidiform mole. In this study, we reported the clinical features of PMD and analyzed its relationship to other severe maternal and/or fetal complications. PATIENT CONCERNS: A 28-year-old female, gravida 2, para 1, was referred to our maternal and child health hospital at 15 weeks + 2 days due to an ultrasonic diagnosis of partial hydatidiform mole. Analysis of chromosome karyotype + mononucleotide-based gene microarray by amniocentesis at the 19th week of gestation showed that fetal amniocentesis chromosome 46, XN, high-resolution chromosome microarray analysis of Affymetrix CytoScan 750K Array revealed a 210 kb fragment deletion in chromosome 2p16.3 containing NRXN1, an OMIM gene, the deleted fragment was derived from a mother with a normal phenotype. The pregnant woman delivered a healthy baby girl at 36 weeks + 5 days. DIAGNOSES: Based on the clinical characteristics, imaging, and genetic test findings, the postoperative diagnosis was PMD. INTERVENTION: Because of "Scar uterus" and "Pregnancy with hydatidiform mole," a 2490 g female infant was delivered by cesarean section at 36 weeks + 5 days of gestation with an Apgar score of 9/9. OUTCOMES: The maternal human chorionic gonadotropin level decreased to the normal range after 10 days of delivery, and the infant was not found abnormal after 3 months of follow-up. LESSONS: From our cases and 19 other cases obtained from the PMD literature review are associated with unique clinical, laboratory, and imaging features compared with a hydatidiform mole, such as stained glass sign, normal serum levels of serum human chorionic gonadotropin, elevated alpha-fetoprotein levels and female fetus.

Eosinophilic/T-cell Chorionic Vasculitis: Its Incidence Is Increasing but It Does Not Appear to Recur in Subsequent Pregnancies.

INTRODUCTION: Eosinophilic/T-cell chorionic vasculitis (E/TCV), an incidental finding primarily in third trimester placentas, is characterized by eosinophils and CD3+ T lymphocytes infiltrating at least 1 chorionic and/or stem villous vessels. Its etiology and clinical significance are unclear. METHODS: Placental pathology reports issued by 8 pediatric-perinatal pathologists at Alberta Children's Hospital were retrieved from the lab information system (2010-2022), and candidate reports were identified using a Perl script searching for "eosinophil." Candidate diagnoses of E/TCV were validated by pathologist review. RESULTS: 38,058 placenta reports from 34,643 patients were reviewed; 328 cases of E/TCV were identified, for an overall incidence of 0.86%. Incidence increased 23% per year, from 0.11% in 2010 to 1.5% in 2021 (P < .01). This temporal change was observed for all pathologists; the incidence of identified multifocality also increased over time (P < .01). Umbilical vascular involvement was exceedingly rare. No variation in incidence was attributable to season. We received more than 1 placenta from 46 mothers with an E/TCV placental diagnosis; examination of >1 placenta did not reveal any mother with >1 E/TCV diagnosis. CONCLUSIONS: The incidence of E/TCV increased steadily over a ~12-year period and no recurrent cases were observed.

Chorioangioma: a single tertiary care center retrospective study.

OBJECTIVES: Chorioangioma represents a challenge due to the rarity of the condition, paucity of sufficient management guidelines, and controversies regarding the best invasive fetal therapy option; most of the scientific evidence for clinical treatment has been limited to case reports. The aim of this retrospective study was to review the natural antenatal history, maternal and fetal complications, and therapeutic modalities used in pregnancies complicated with placental chorioangioma at a single Center. METHODS: This retrospective study was conducted at King Faisal Specialist Hospital and Research Center (KFSH&RC) in Riyadh, Saudi Arabia. Our study population included all pregnancies with ultrasound features of chorioangioma, or histologically confirmed chorioangiomas, between January 2010 and December 2019. Data were collected from the patients' medical records, including the ultrasound reports and histopathology results. All subjects were kept anonymous; case numbers were used as identifiers. Data collected by the investigators were entered into Excel worksheets in an encrypted format. A MEDLINE database was used to retrieve 32 articles for literature review. RESULTS: Over a 10-year period between January 2010 and December 2019, 11 cases of chorioangioma were identified. Ultrasound remains the gold standard for diagnosis and follow-up of the pregnancy. Seven of the 11 cases were detected by ultrasound, allowing proper fetal surveillance and antenatal follow-up. Of the remaining six patients, one underwent radiofrequency ablation, two underwent intrauterine transfusion for fetal anemia due to placenta chorioangioma, one had vascular embolization with an adhesive material, and two were managed conservatively until term with ultrasound surveillance. CONCLUSIONS: Ultrasound remains the gold standard modality for prenatal diagnosis and follow-up of pregnancies with suspected chorioangiomas. Tumor size and vascularity play a significant role in the development of maternal-fetal complications and the success of fetal interventions. To determine the superior modality of fetal intervention mandates more data and research; nevertheless, Fetoscopic Laser Photocoagulation and embolization with adhesive material seem to be a lead choice, with reasonable fetal survival.

Serum amyloid A1 and pregnancy zone protein in pregnancy complications and correlation with markers of placental dysfunction.

BACKGROUND: Hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, and chronic hypertension), diabetes mellitus, and placental dysfunction confer an increased risk of long-term maternal cardiovascular disease. Preeclampsia is also associated with acute atherosis that involves lesions of uteroplacental spiral arteries, resembling early stages of atherosclerosis. Serum amyloid A1 is involved in hypercoagulability and atherosclerosis and may aggregate into amyloid-aggregations of misfolded proteins. Pregnancy zone protein may inhibit amyloid aggregation. Amyloid is involved in Alzheimer's disease and cardiovascular disease; it has been identified in preeclampsia, but its role in preeclampsia pathophysiology is unclear. OBJECTIVE: We hypothesized that serum amyloid A1 would be increased and pregnancy zone protein decreased in hypertensive disorders of pregnancy and diabetic pregnancies and that serum amyloid A1 and pregnancy zone protein would correlate with placental dysfunction markers (fetal growth restriction and dysregulated angiogenic biomarkers) and acute atherosis. STUDY DESIGN: Serum amyloid A1 is measurable in both the serum and plasma. In our study, plasma from 549 pregnancies (normotensive, euglycemic controls: 258; early-onset preeclampsia: 71; late-onset preeclampsia: 98; gestational hypertension: 30; chronic hypertension: 9; diabetes mellitus: 83) was assayed for serum amyloid A1 and pregnancy zone protein. The serum levels of angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were available for 547 pregnancies, and the results of acute atherosis evaluation were available for 313 pregnancies. The clinical characteristics and circulating biomarkers were compared between the pregnancy groups using the Mann-Whitney U, chi-squared, or Fisher exact test as appropriate. Spearman's rho was calculated for assessing correlations. RESULTS: In early-onset preeclampsia, serum amyloid A1 was increased compared with controls (17.1 vs 5.1 µg/mL, P<.001), whereas pregnancy zone protein was decreased (590 vs 892 µg/mL, P=.002). Pregnancy zone protein was also decreased in diabetes compared with controls (683 vs 892 µg/mL, P=.01). Serum amyloid A1 was associated with placental dysfunction (fetal growth restriction, elevated soluble fms-like tyrosine kinase-1 to placental growth factor ratio). Pregnancy zone protein correlated negatively with soluble fms-like tyrosine kinase-1 to placental growth factor ratio in all study groups. Acute atherosis was not associated with serum amyloid A1 or pregnancy zone protein. CONCLUSION: Proteins involved in atherosclerosis, hypercoagulability, and protein misfolding are dysregulated in early-onset preeclampsia and placental dysfunction, which links them and potentially contributes to future maternal cardiovascular disease.

Shallow Placentation: A Distinct Category of Placental Lesions.

OBJECTIVE: Shallow placental implantation (SPI) features placental maldistribution of extravillous trophoblasts and includes excessive amount of extravillous trophoblasts, chorionic microcysts in the membranes and chorionic disc, and decidual clusters of multinucleate trophoblasts. The histological lesions were previously and individually reported in association with various clinical and placental abnormalities. This retrospective statistical analysis of a large placental database from high-risk pregnancy statistically compares placentas with and without a composite group of features of SPI. STUDY DESIGN: Twenty-four independent abnormal clinical and 44 other than SPI placental phenotypes were compared between 4,930 placentas without (group 1) and 1,283 placentas with one or more histological features of SPI (composite SPI group; group 2). Placentas were received for pathology examination at a discretion of obstetricians. Placental lesion terminology was consistent with the Amsterdam criteria, with addition of other lesions described more recently. RESULTS: Cases of group 2 featured statistically and significantly (p < 0.001after Bonferroni's correction) more common than group 1 on the following measures: gestational hypertension, preeclampsia, oligohydramnios, polyhydramnios, abnormal Dopplers, induction of labor, cesarean section, perinatal mortality, fetal growth restriction, stay in neonatal intensive care unit (NICU), congenital malformation, deep meconium penetration, intravillous hemorrhage, villous infarction, membrane laminar necrosis, fetal blood erythroblastosis, decidual arteriopathy (hypertrophic and atherosis), chronic hypoxic injury (uterine and postuterine), intervillous thrombus, segmental and global fetal vascular malperfusion, various umbilical cord abnormalities, and basal plate myometrial fibers. CONCLUSION: SPI placentas were statistically and significantly associated with 48% abnormal independent clinical and 51% independent abnormal placental phenotypes such as acute and chronic hypoxic lesions, fetal vascular malperfusion, umbilical cord abnormalities, and basal plate myometrial fibers among others. Therefore, SPI should be regarded as a category of placental lesions related to maternal vascular malperfusion and the "Great Obstetrical Syndromes." KEY POINTS: · SPI reflects abnormal distribution of extravillous trophoblasts.. · SPI features abnormal clinical and placental phenotypes.. · SPI portends increased risk of complicated perinatal outcome..

Fetal Vascular Ectasia Can be an Artifact of Placental Fixation.

BACKGROUND: Placentas from outlying hospitals are formalin-fixed en route to our laboratory. We identified that chorionic, stem villus, and umbilical vessels in these fixed placentas are ectatic with greater frequency than in our in-house fresh placentas. METHODS: We searched our LIS for third trimester placentas using keywords "ectasia" or "ectatic" over a 12-month period. We fixed incoming in-house placentas over a 2-week period for 24-72 hours and tabulated the presence or absence of vascular ectasia as defined by Parast et al, 2008. RESULTS: The LIS search identified 61% of placental cases from outlying hospitals that had ectatic vessels vs 3% of in-house placentas (P < .001). Of 38 placentas fixed in a 2-week period, 45% had ectatic chorionic or stem villus vessels and 21% had umbilical vessel ectasia. In comparison, in the 2 subsequent weeks, 3.8% (P < .001) of fresh placentas had vascular ectasia. CONCLUSION: These data suggest that large fetal vessels in the placenta become engorged with blood at delivery and, if fixed soon after delivery, remain ectatic and congested when processed for pathology. The identification of artifactual ectasia is important because fetal vessel ectasia can suggest the presence of fetal vascular malperfusion (FVM) if diagnostic signs of FVM are present.