Prospective study of malaria in pregnancy, placental and congenital malaria in Northwest Colombia.

BACKGROUND: Pregnancy Associated Malaria (PAM) include malaria in pregnancy (MiP), placental malaria (PM), and congenital malaria (CM). The evidence available in Colombia on PAM focuses on one of the presentations (MiP, PM or CM), and no study longitudinally analyses the infection from the pregnant woman, passing through the placenta, until culminating in the newborn. This study determined the frequency of MiP, PM, and CM caused by Plasmodium vivax, Plasmodium falciparum, or mixed infections, according to Thick Blood Smear (TBS) and quantitative Polymerase Chain Reaction (qPCR). Identifying associated factors of PAM and clinical-epidemiological outcomes in northwestern Colombia. METHODS: Prospective study of 431 pregnant women, their placenta, and newborns registered in the data bank of the research Group "Salud y Comunidad César Uribe Piedrahíta" which collected information between 2014 and 2020 in endemic municipalities of the departments of Córdoba and Antioquia. The frequency of infection was determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Student t-test, prevalence ratios, and control for confounding variables by log-binomial regression. RESULTS: The frequency of MiP was 22.3% (4.6% using TBS), PM 24.8% (1.4% using TBS), and CM 11.8% (0% using TBS). Using TBS predominated P. vivax. Using qPCR the proportions of P. vivax and P. falciparum were similar for MiP and PM, but P. falciparum predominated in CM. The frequency was higher in nulliparous, and women with previous malaria. The main clinical effects of PAM were anaemia, low birth weight, and abnormal APGAR score. CONCLUSIONS: The magnitude of infections was not detected with TBS because most cases were submicroscopic (TBS-negative, qPCR-positive). This confirmed the importance of improving the molecular detection of cases. PAM continue being underestimated in the country due to that in Colombia the control programme is based on TBS, despite its outcomes on maternal, and congenital health.

Impact of villitis of unknown etiology and adverse acute neonatal outcomes in Eastern Ontario.

INTRODUCTION: Villitis of unknown etiology (VUE) is a histopathological lesion associated with adverse neonatal outcomes. We seek to define the obscure relationship between the severity and distribution of VUE and adverse neonatal outcomes. METHODS: A retrospective chart review was conducted of pathologic findings from singleton placentas diagnosed with VUE between 2013 and 2019. Control placentas were matched 1:1 for gestational age and presence/absence of fetal IUGR. Neonatal outcomes of interest included: newborn resuscitation, NICU admission, Apgar scores and cord blood acidosis. Odds ratio and 95 % confidence intervals were calculated with controls as the reference. RESULTS: 452 placentas were included. 35 % of pregnancies were complicated by IUGR. When analyzed by severity (low-grade: OR = 4.75 [2.86-8.14]; high-grade: OR = 4.76 [2.71-8.79]) and distribution (focal: OR = 5.24 [2.87-10.17]; multifocal: OR = 4.90 [2.90-8.59]), VUE was significantly associated with need for newborn resuscitation. No other neonatal outcomes of interest were significantly associated with VUE diagnosis. DISCUSSION: We determined a statistically significant association between VUE severity and distribution and the need for newborn resuscitation. VUE lesions were not associated with any additional neonatal outcomes of interest. Further studies with larger sample sizes are required to confirm these associations for obstetric and neonatal case management.

Prenatal diagnosis of bilobate placenta: incidence, risk factors and impact on pregnancy outcomes.

OBJECTIVES: To investigate the incidence and risk factors of bilobate placenta, as well as to assess its impact on preeclampsia (PE), preterm delivery (PTD) and small-for-gestational age (SGA) neonates. METHODS: A prospective study of singleton pregnancies, undergoing routine anomaly scan at 20+0-23+6 gestational weeks, was conducted, between 2018 and 2022. The impact of prenatally diagnosed bilobate placenta on PE, PTD and SGA was assessed. Multivariate logistic regression models were employed to assess the independent association between bilobate placenta and the main pregnancy outcomes, using specific confounders. Additionally, a risk factor analysis was performed. RESULTS: The study population included 6,454 pregnancies; the incidence of prenatally diagnosed bilobate placenta was 2.0 % (n=129). Bilobate placenta was associated with PE (aOR: 1.721; 95 % CI: 1.014-2.922), while no statistically significant association was found between this anatomical variation and SGA (aOR: 1.059; 95 % CI: 0.665-1.686) or PTD (aOR: 1.317; 95 % CI: 0.773-2.246). Furthermore, pregnancies with prenatally diagnosed bilobate placenta had an increased prevalence of abnormal cord insertion (marginal or velamentous) (9.8 vs. 27.1 %; p<0.001) and increased mean UtA PI z-score (0.03 vs. 0.23; p=0.039). Conception via ART (aOR: 3.669; 95 % CI: 2.248-5.989), previous history of 1st trimester miscarriage (aOR: 1.814; 95 % CI: 1.218-2.700) and advancing maternal age (aOR: 1.069; 95 % CI: 1.031-1.110) were identified as major risk factors for bilobate placenta. CONCLUSIONS: Bilobate placenta, excluding cases of co-existing vasa previa, is associated with higher incidence of PE, increased mean UtA PI z-score and higher probability of abnormal cord insertion, but not with increased risk for SGA or PTD. It is more common in pregnancies following ART and in women with a previous 1st trimester miscarriage.

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

INTRODUCTION: Women 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, Maori and New Zealand (NZ) European women in Aotearoa NZ, with a focus on women of South Asian ethnicity. METHODS: Placental 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. RESULTS: 790 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 Maori (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 Maori (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). DISCUSSION: Differences 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.

Placental chorioangioma and pregnancy outcome: a ten-year retrospective study in a tertiary referral centre.

BACKGROUND: Placental chorioangioma is a rare disorder in pregnancy. We retrospectively reviewed the perinatal complications and long-term outcomes in pregnancies with placental chorioangioma and evaluated the factors affecting disease prognosis. METHODS: We reviewed pregnant women who delivered at our hospital in the past decade and whose diagnosis of placental chorioangioma was confirmed by pathological diagnosis. Information on maternal demographics, prenatal sonographic findings and perinatal outcomes was obtained by reviewing the medical records. In the latter part of the study, follow-up of children was conducted by phone interview. RESULTS: In the 10 years from August 2008 to December 2018, 175 cases(0.17%) were identified as placental chorioangioma histologically and 44(0.04%) of them were large chorioangiomas. Nearly one-third of cases with large chorioangiomas were associated with severe maternal and fetal complications or required prenatal intervention. Although one-fifth of fetuses/newborns complicated with large chorioangiomas were lost perinatally, the long-term prognosis for surviving fetuses was generally good. Further statistical analysis revealed that tumor size and location affect prognosis. CONCLUSION: Placental chorioangioma may cause an unfavorable perinatal outcome. Regular ultrasound monitoring can provide the tumor characteristics which can be referred to for predicting the tendency of those complications and indicate when intervention may be necessary. It is not clear which factors lead to complications with fetal damage as the main manifestation or polyhydramnios as the main manifestation.

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.

Placental Histopathologic Findings of a Large Cohort of Patients With SARS-CoV-2 Infection During Pregnancy.

Pregnant individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at a higher risk for adverse pregnancy outcomes. Previous small cohort studies have shown increased frequency of placental lesions associated with maternal vascular malperfusion, fetal vascular malperfusion, and inflammation among patients with SARS-CoV-2, without controlling for cardiometabolic risk factors among many such patients. We aimed to evaluate whether SARS-CoV-2 infection during pregnancy is independently associated with placental abnormalities when controlling for risk factors that could affect placental histopathology. Retrospective cohort study of placentas from singleton pregnancies in Kaiser Permanente Northern California from March to December 2020. Pathologic findings were compared among those with confirmed cases of SARS-CoV-2 during pregnancy and those without. We examined the association between SARS-CoV-2 infection and categorical placental pathologies, controlling for maternal age, gestational age, prepregnancy body mass index, gestational hypertension, preeclampsia/eclampsia, preexisting diabetes, history of thrombosis, and stillbirth. A total of 2,989 singleton gestation placentas were analyzed, 416 (13%) from pregnancies with SARS-CoV-2 infection and 2,573 (86%) from those without infection. Among placentas from pregnancies with SARS-CoV-2, 54.8% had evidence of inflammation, 27.1% maternal malperfusion abnormality, 20.7% massive perivillous fibrin or chronic villitis, 17.3% villous capillary abnormality, and 15.1% fetal malperfusion. After controlling for risks factors and stratifying interval time between SARS-CoV-2 infection and delivery, no association was found between placental abnormalities and SARS-CoV-2 infection during pregnancy. SARS-CoV-2 infection was not associated with an increased risk of placentally mediated adverse outcomes during pregnancy, compared with placentas sent for other indications, in this large diverse cohort.

Machine learning-based placental clusters and their associations with adverse pregnancy outcomes.

BACKGROUND: Placental abnormalities have been described in clinical convenience samples, with predominately adverse outcomes. Few studies have described placental patterns in unselected samples. OBJECTIVE: We aimed to investigate associations between co-occurring placental features and adverse pregnancy outcomes in a prospective cohort of singletons. METHODS: Data were from the Safe Passage study (U.S. and South Africa, 2007-2015). Before 24 weeks' gestation, participants were randomly invited to donate placental tissue at delivery for blinded, standardised pathological examination. We used hierarchical clustering to construct statistically derived groups using 60 placental features. We estimated associations between the placental clusters and select adverse pregnancy outcomes, expressed as unadjusted and adjusted risk ratios (RRs) and robust 95% confidence intervals (CI). RESULTS: We selected a 7-cluster model. After collapsing 2 clusters to form the reference group, we labelled the resulting 6 analytic clusters according to the overarching category of their most predominant feature(s): severe maternal vascular malperfusion (n = 117), fetal vascular malperfusion (n = 222), other vascular malperfusion (n = 516), inflammation 1 (n = 269), inflammation 2 (n = 175), and normal (n = 706). Risks for all outcomes were elevated in the severe maternal vascular malperfusion cluster. For instance, in unadjusted analyses, this cluster had 12 times the risk of stillbirth (RR 12.07, 95% CI 4.20, 34.68) and an almost doubling in the risk of preterm delivery (RR 1.93, 95% CI 1.27, 2.93) compared with the normal cluster. Small infant size was more common among the abnormal clusters, with the highest unadjusted RRs observed in the fetal vascular malperfusion cluster (small for gestational age birth RR 2.99, 95% CI 2.24, 3.98, head circumference <10th percentile RR 2.86, 95% CI 1.60, 5.12). Upon adjustment for known risk factors, most RRs attenuated but remained >1. CONCLUSION: Our study adds to the growing body of epidemiologic research, finding adverse pregnancy outcomes may occur through etiologic mechanisms involving co-occurring placental abnormalities.

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.

Placental delayed villous maturation is associated with fetal congenital heart disease.

BACKGROUND: The placenta is crucial for the overall development and lifelong health of the fetus. Abnormal placental development and function occur in pregnancies with fetal congenital heart disease. However, studies that use standardized diagnostic criteria and incorporate control populations are lacking. This limits the generalizability of current research and the ability to determine the specific placental abnormalities associated with congenital heart disease. OBJECTIVE: This study applied consensus statement guidelines (known as the Amsterdam criteria) for placental pathology interpretation to compare the frequency and pattern of abnormalities in pregnancies with fetal congenital heart disease to demographically matched control pregnancies and evaluate for differences in placental abnormalities by cardiac physiology. STUDY DESIGN: A single-center retrospective cohort study was conducted from January 2013 to June 2019. Infants with a prenatal diagnosis of moderate-severe congenital heart disease who were born at ≥37 weeks of gestation were included. A control group born at ≥37 weeks of gestation but without fetal congenital heart disease or other major pregnancy complications was matched to the congenital heart disease group on maternal race and ethnicity and infant sex. Using the Amsterdam criteria, placental pathology findings were categorized as delayed villous maturation, maternal vascular malperfusion, fetal vascular malperfusion, and inflammatory lesions. The frequency of placental abnormalities was compared between groups, and logistic regression was performed to evaluate the association of clinical and sociodemographic factors with delayed villous maturation, maternal vascular malperfusion, and fetal vascular malperfusion. RESULTS: There were 194 pregnancies with fetal congenital heart disease and 105 controls included, of whom 83% in the congenital heart disease group and 82% in the control group were of non-Hispanic White race and ethnicity. Compared with controls, pregnancies with fetal congenital heart disease had higher rates of delayed villous maturation (6% vs 19%; P<.001) and maternal vascular malperfusion (19% vs 34%; P=.007) but not fetal vascular malperfusion (6% vs 10%; P=.23). Infants with congenital heart disease with 2-ventricle anatomy displayed the highest odds of delayed villous maturation compared with controls (odds ratio, 5.5; 95% confidence interval, 2.2-15.7; P<.01). Maternal vascular malperfusion was 2.2 times higher (P=.02) for infants with 2-ventricle anatomy and 2.9 times higher (P=.02) for infants with single-ventricle physiology with pulmonic obstruction. Within the congenital heart disease group, delayed villous maturation was associated with higher maternal body mass index, polyhydramnios, larger infant birth head circumference, and infant respiratory support in the delivery room, whereas maternal vascular malperfusion was associated with oligohydramnios. In multivariable models adjusting for cardiac diagnosis, associations of delayed villous maturation persisted for infant birth head circumference (odds ratio, 1.2; 95% confidence interval, 1.0-1.5; P=.02) and infant respiratory support in the delivery room (odds ratio, 3.0; 95% confidence interval, 1.3-6.5; P=.007). CONCLUSION: Pregnancies with fetal congenital heart disease displayed higher rates of delayed villous maturation and maternal vascular malperfusion than controls, suggesting that placental maldevelopment may relate to maternal factors. Future investigations are needed to determine the association of these abnormalities with postnatal infant outcomes.

Cumulative effect of maternal vascular malperfusion types in the placenta on adverse pregnancy outcomes.

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.

Association of distinct features of villitis of unknown etiology histopathology and fetal growth restriction diagnosis in a retrospective cohort from Eastern Ontario.

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.

Chronic villitis of unknown aetiology: an Australian institution's 5-year experience.

Villitis of unknown aetiology (VUE) is a chronic inflammatory condition of the placenta that is associated with increased morbidity and mortality in perinatal medicine. The cause remains elusive and recent studies have explored immune-mediated, infectious and environmental triggers in the pathogenesis of VUE. The objective of this study was to identify the characteristics of VUE diagnoses at Mater Mothers' Hospital over a 5-year period, including any association with seasons, maternal age and histological patterns of the disorder. We retrospectively reviewed reports for placentas sent to Mater Pathology, Brisbane, over 5 years (December 2015 to November 2020). Case level data were retrieved including maternal age, the month of delivery, gestational age, parity, VUE status, recurrence, histopathological subtype and grade. Univariable and multivariable logistic regression was used to estimate the unadjusted and adjusted association between VUE and season, maternal age and trimester at delivery. While more placentas were examined during summer than winter (p=0.005), there was no evidence of seasonal variation in the incidence of VUE over the 5 years (p=0.17). Both univariable and multivariable logistic regression analyses showed that VUE increased with maternal age (p<0.001) and gestational age (9.8% of examined placentas in the third trimester compared to 2.1% in first and second trimesters, p<0.001). Seven of 714 women with VUE (0.98%) had one or more recurrences of the condition within the study period. Of these, VUE was of lower grade in two of the three women who were prescribed aspirin in the subsequent pregnancy. Furthermore, basal VUE without basal myometrial fibres (6.6%), was over-represented among clinically morbidly adherent placentas (MAP) reported in this cohort. Our study does not show evidence of a seasonal variation in VUE incidence. The immune-mediated pathogenesis of VUE is favoured, with our data showing increased rates of the condition as maternal age increases.

Placental vascular malperfusion lesions in fetal congenital heart disease.

BACKGROUND: Fetuses with congenital heart disease are at increased risk of perinatal morbidity and mortality, which is highly influenced by their prenatal health. Placental function is vital for the health of the fetus, but increased rates of pathologic lesions of the placenta have been observed in pregnancies complicated by fetal congenital heart disease. OBJECTIVE: This study aimed to determine the prevalence of both gross and histologic placental pathologies in a cohort of pregnancies complicated by fetal congenital heart disease vs healthy controls using the Amsterdam Placental Workshop Group Consensus Statement sampling and definitions of placental lesions. STUDY DESIGN: This single-center retrospective cohort study included placental examinations from pregnancies diagnosed prenatally with fetal congenital heart disease between 2010 and 2019; moreover, control placentas were collected from pregnancies without maternal or fetal complications. Placentas were sampled and evaluated according to the Amsterdam Placental Workshop Group Consensus Statement and gross and histopathologic diagnoses determined. RESULTS: Approximately 80% of fetuses diagnosed with congenital heart disease (n=305) had a placental examination for comparison with controls (n=40). Of note, 239 placentas (78%) in the group with fetal congenital heart disease had at least 1 gross or histopathologic lesion compared with 11 placentas (28%) in the control group (P<.01). One-third of placentas complicated by fetal congenital heart disease met the criteria for small for gestational age, and 48% of placentas had one or more chronic lesions, including maternal vascular malperfusion (23% vs 0%; P<.01), villitis of unknown etiology (22% vs 0%; P<.01), fetal vascular malperfusion (20% vs 0%; P<.01), and other chronic lesions (16% vs 0%; P<.01). Acute inflammation was equally present in both the group with fetal congenital heart disease and the control group (28% vs 28%; P=1.00). Although gestational age and birthweight z score were similar between the 2 groups, birth head circumference was 1.5 cm less in pregnancies complicated by fetal congenital heart disease with a significantly lower z score compared with the control group (-0.52±1.22 vs 0.06±0.69; P<.01). CONCLUSION: Vascular malperfusion lesions and chronic forms of inflammation occur at markedly higher rates in placentas complicated by fetal congenital heart disease, which may contribute to the decreased head circumference at birth. Further work in neuroplacentology is needed to explore connections among cardiac defects, placental vascular malperfusion lesions, and fetal brain development.

Recurrence risk of villitis of unknown etiology: Analysis of a large retrospective cohort study, systematic review and meta-analysis.

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%.

Symptomatic versus asymptomatic COVID-19: does it impact placental vasculopathy?

This study sought to assess the impact of COVID-19 on placental vasculature in the context of maternal symptomatology - comparing asymptomatic to symptomatic pregnant patients - and disease severity - comparing pregnant patients with mild, moderate, severe, and critical COVID-19 infection. PCR-confirmed COVID-19 positive pregnant patients in a single health system who delivered between 3/2020-5/2021 included. All patients had positive COVID test and delivered during the study period. Primary outcome was incidence of any vascular malperfusion on placental pathology. Secondary outcomes were FVM and MVM on placental pathology. Placental pathology compared between symptomatic (sCOVID) and asymptomatic (aCOVID) patients. Secondary analysis of symptomatic patients, comparing placental pathology between mild disease(mCOVID) and worse disease(moderate, severe, or critical-defined by 2020 NIH guidelines) (dCOVID), also performed. Of 112 patients, 53 (47%) had symptoms. Twenty-seven (24.1%) patients had evidence of vascular malperfusion; 26 (23.2%) had MVM. When comparing aCOVID and sCOVID patients, no difference in rate of vascular malperfusion identified, nor any differences in rates of FVM or MVM. Among sCOVID patients (n = 53), 39 (74%) had mCOVID and 14 (26%) had dCOVID (moderate n = 4, severe n = 9, critical n = 1). Patients with dCOVID had earlier median delivery GA (37.4wks vs 39.2wks, p = .03). No difference in latency from diagnosis to delivery seen between mCOVID and dCOVID groups (4.4 vs 3.0wks, p = .96). Twelve (30.8%) patients had vascular malperfusion on pathology, all had mCOVID (p = .02). Eleven (28.2%) mCOVID patients had MVM; no dCOVID patients had evidence of vascular malperfusion (p = .03). No difference in FVM was found between cohorts. Symptomatic COVID-19 infection did not impact placental vasculature differently than asymptomatic infection, even when stratifying by trimester of infection. Among pregnant patients with symptomatic COVID-19, mild disease was associated with placental vascular changes on the maternal side while severe disease was not. Further studies are needed to understand the implications of these findings.

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF.

BACKGROUND: Ischaemic placental disease (IPD) affects 16%-23% of pregnancies in the United States. In vitro fertilisation (IVF) is a risk factor for IPD, and the magnitude of increase in risk differs for individuals using donor oocytes (donor IVF) versus their own oocytes (autologous IVF). In addition, multifoetal gestations, which are more common in IVF than non-IVF pregnancies, also are a risk factor for IPD. OBJECTIVE: To quantify the contribution of multifoetal gestations to the association between IVF and IPD. METHODS: We conducted a retrospective cohort study at a tertiary hospital from 1 January, 2000 to 1 August 2018 using electronic medical records and state vital statistics data. IPD was defined as preeclampsia, placental abruption, small for gestational age (SGA) birth or an intrauterine foetal demise due to placental insufficiency. We used mediation analysis to decompose the total effect of IVF on IPD into a natural direct effect and an indirect effect through multifoetal gestations. We repeated the analyses separately for donor and autologous IVF. All models were adjusted for maternal age, race, parity, insurance, year of delivery and account for multiple pregnancies per person. RESULTS: We identified 86,514 deliveries, of which 281 resulted from donor IVF and 4173 resulted from autologous IVF. IVF pregnancies had 1.99 (95% CI 1.88, 2.10) times the risk of IPD compared to non-IVF pregnancies, and 75.5% of this increased risk was mediated by multifoetal gestations. Autologous IVF pregnancies had 1.95 (95% CI 1.84, 2.07) times the risk of IPD compared to non-IVF pregnancies, and the per cent mediated was 78.8%. Donor IVF pregnancies had 2.50 (95% CI 2.09, 2.92) times the risk of IPD, but the per cent mediated was 37.5%. CONCLUSION: The majority of the association between autologous IVF and IPD was mediated through multifoetal gestations; however, this was not the case for donor IVF pregnancies.

Placental findings in singleton stillbirths: a case-control study from a tertiary-care center in India.

OBJECTIVES: Placental examination in a case of stillbirth can provide insight into causative/associated factors with fetal demise. The aim of this study was to compare placental and umbilical cord pathologies in singleton stillbirth and livebirth placentas, and to find prevalence of various associated maternal and fetal clinical factors. METHODS: This case-control study was conducted at a tertiary-care center in India over a period of 20 months. About 250 women who delivered stillborn fetus ≥28 weeks' gestation and 250 maternal-age-matched controls were recruited. Sociodemographic and clinical details were noted and placental gross and microscopic examination was done. Placental findings were compared between stillbirth and livebirth (overall), preterm stillbirth and preterm livebirth as well as term stillbirth and term livebirth in six categories - placenta gross, cord gross, membranes gross, maternal vascular malperfusion, fetal vascular malperfusion and inflammatory response. Prevalence of 11 maternal and fetal factors were studied in all categories of placental findings in both livebirth and stillbirth. RESULTS: Placental findings in all six categories were significantly associated with stillbirths (p<0.05). The placental findings associated with stillbirth with highest odds included placental hypoplasia (OR 9.77, 95% CI 5.46-17.46), necrotizing chorioamnionitis (OR 9.30, 95% CI 1.17-73.96) and avascular villi (OR 8.45, 95% CI 3.53-20.25). More than half of the women with stillbirths had medical disorders (n=130, 52.0%) and the most prevalent was hypertensive disorder (n=45, 18.0%). CONCLUSIONS: Changes in placenta are associated with development of stillbirth. Therefore, antenatal investigations to identify placental dysfunction should be investigated to determine whether these reduce stillbirth. Also, placental examination in a case of stillbirth can detect/diagnose many maternal/fetal conditions and thereby can help in preventing future stillbirths.