Placental Malperfusion Lesions Research Articles

Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana

Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study.This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion.Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group.Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.

Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions

To assess obstetric outcomes and placental findings in pregnancies attained by invitro fertilization (IVF) in patients with diminished ovarian reserve (DOR). Retrospective cohort study. University-affiliated tertiary hospital. DOR, defined as an antral follicle count (AFC) of 6 or less (DOR group), compared with patients with no DOR and an antral count above 6 (control group). Live singleton births after IVF between 2009 and2017. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, as categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes. A total of 110 deliveries of patients with DOR were compared with 772 controls. Maternal age was higher in the DOR group than in the control group (36.3 ± 4.4 years vs. 35.3 ± 4.1 years, P=.02). Patients with DOR were more likely to have a diagnosis of endometriosis (P=.02) and less likely to have a diagnosis of male factor (P<.001), ovulation disorder (P<.001), or tubal factor (P=.04), or a transfer of a blastocyte (P=.007). After adjustment for confounders, pregnancies in the DOR group were notable for a significantly higher rate of preeclampsia (8.1% vs. 2.7%, adjusted odds ratio: 3.05, 95% confidence interval: 1.33-6.97). On placental examination, DOR was associated with a higher rate of fetal vasculopathy (P=.01) and multiple fetal vascular malperfusion lesions (P=.03), and a lower rate of circummarginate insertion (P=.01) and intervillous thrombosis (P=.02). DOR, specifically defined as an AFC of 6 or less, is associated with a higher incidence of preeclampsia and multiple placental fetal vascular lesions.

Patterns in Prenatal Physical Activity and Sedentary Behavior: Associations With Blood Pressure and Placental Features in the MoMHealth Cohort.

Moderate to vigorous physical activity (MVPA) and sedentary behavior (SED) are associated with blood pressure (BP) and adverse pregnancy outcomes. The authors investigated associations of prenatal MVPA and SED patterns with BP and with placental malperfusion features. Women enrolled in this prospective cohort study in the first trimester. MVPA, SED, and BP were measured objectively each trimester. MVPA and SED trajectories were constructed. Placental examinations were conducted in a subset. Associations of trajectories with BPs were assessed with linear regression adjusted for age, race, education, prepregnancy body mass index, and gestational age. Associations with placental malperfusion lesions and weight were adjusted for key covariates. One hundred eleven participants were included; placental exams were available in 50. Participants with high (vs low) SED were younger and more likely to have adverse pregnancy outcomes. High SED (vs low) was associated with higher first trimester systolic (β = 5.3; 95% confidence interval, 0.0 to 10.6) and diastolic (β = 5.0; 95% confidence interval, 1.4 to 8.6) and higher second trimester diastolic (β = 4.9; 95% confidence interval, 1.6 to 8.2) BP. Medium and high MVPA groups were associated with lower postpartum diastolic BP. Trajectories were not associated with placental malperfusion. MVPA and SED patterns were differentially associated with prenatal and postpartum BP. Encouraging favorable levels of both might help women achieve lower BP during and after pregnancy.

A New Approach for Classifying Fetal Growth Restriction.

Fetal growth restriction is commonly defined using small for gestational age (SGA) birth (birthweight < 10th percentile) as a proxy, but this approach is problematic because most SGA infants are small but healthy. In this proof-of-concept study, we sought to develop a new approach for identifying fetal growth restriction at birth that combines information on multiple, imperfect measures of fetal growth restriction in a probabilistic manner. We combined information on birthweight, placental weight, placental malperfusion lesions, maternal disease, and fetal acidemia using latent profile analysis to classify fetal growth in births at the Royal Victoria Hospital in Montreal, Canada, 2001-2009. We examined the clinical characteristics and health outcomes of infants classified as growth-restricted and nongrowth-restricted by our model, and among the subgroup of growth-restricted infants who had a birthweight ≥10th percentile (i.e., would have been missed by the conventional SGA proxy). Among 26,077 births, 345 (1.3%) were classified as growth-restricted by our latent profile model. Growth-restricted infants were more likely than nongrowth-restricted infants to have an Apgar score <7 (10% vs. 2%), have hypoglycemia at birth (17% vs. 3%), require neonatal intensive care unit admission (59% vs. 6%), die in the perinatal period (3.8% vs. 0.2%), and require an emergency cesarean delivery (42% vs. 15%). Risks remained elevated in growth-restricted infants who were not SGA, suggesting our model identified at-risk infants not detected using the SGA proxy. Latent profile analysis is a promising strategy for classifying growth restriction at birth in fetal growth restriction research.

Passively inhaled tobacco smoke - pregnancy and neonatal outcomes in correlation with placental histopathology

IntroductionWe aimed to investigate the effect of maternal passive smoking (MPS) during pregnancy-on placental pathology and pregnancy outcomes. MethodsA prospective case-control study. We recruited low-risk laboring women at 37+0–41 + 0 weeks between 9/2019–7/2020. MPS was defined as exposure to in-house spouse tobacco smoking of >20 cigarettes/day in the absence of maternal active-smoking. In attempt to “purify” the effect of MPS on placental pathology-we excluded cases with preeclampsia, diabetes, suspected fetal growth restriction (FGR), preterm labor, and illicit drug use. Maternal characteristics, pregnancy outcomes, and placental pathology were compared between the MPS group and a control group matched for gestational age, maternal age, and delivery date. Placental lesions were classified according to the “Amsterdam” criteria. The study was powered to detect a 33% difference in placental malperfusion lesions. Multivariable regression was performed to identify independent associations with placental malperfusion lesions. ResultsIn labor, the MPS group (n = 115) had higher rates of meconium stained amniotic fluid (MSAF, p < 0.001) and non-reassuring fetal heart-rate (NRFHR,p = 0.006), compared to controls (n = 115). Neonates in the MPS group had higher rates of undiagnosed FGR (p = 0.01) and NICU admissions (p = 0.004). The MPS group had higher rates of placental-hypoplasia (p = 0.02) and fetal vascular malperfusion (FVM) lesions (p = 0.04). In regression analysis MPS was associated with FVM lesions independent of background confounders (aOR = 1.24 95% CI 1.10–2.65). DiscussionIn otherwise low-risk pregnancies, MPS was associated with higher rates of MSAF, NRFHR, undiagnosed FGR, and NICU admissions, probably mediated via placental FVM. These worrisome findings mandate patient counseling and further investigation in larger population-based studies.

458 Maternal passive-smoking during pregnancy. the effect on pregnancy outcomes and placental-pathology. A prospective case-control study

The effect of maternal passive smoking (MPS) during pregnancy is difficult to investigate and was poorly studied before. This study was designed to investigate the effects of MPS during pregnancy- on placental pathology and pregnancy outcomes. We performed a prospective case-control study. We recruited low-risk laboring women at 37+0 to 41+0 weeks between 9/2019-7/2020. MPS was defined as exposure to a spouse that reported in-house tobacco smoking of > 20 cigarettes/day in the absence of maternal active smoking. In an attempt to "purify" the effect of MPS - we excluded cases with preeclampsia, diabetes, suspected fetal growth restriction (FGR), preterm labor, and illicit drug use. Maternal characteristics, pregnancy outcomes, and placental pathology were compared between the MPS group and a control group matched for gestational age, maternal age, and delivery date. Placental lesions were classified according to “Amsterdam” criteria. The study was powered to detect a 33% difference in placental malperfusion lesion and was calculated as 115 cases in each group. Multivariable regression analysis was performed to identify independent associations with placental malperfusion lesions. In labor, the MPS group (n=115) had higher rates of meconium-stained amniotic fluid (MSAF, p<0.001) and non-reassuring fetal heart rate (NRFHR) that necessitated immediate delivery (p=0.03), compared to controls (n=115). Neonates in the MPS group had higher rates of undiagnosed FGR (p=0.01) and NICU admissions (p=0.004). In placental pathology, the MPS group had higher rates of placental hypoplasia (p=0.02) and fetal vascular malperfusion (FVM) lesions (p=0.04). In regression analysis MPS was associated with FVM lesions independent of background confounders (aOR=2.3 95% CI 1.26-6.34). In otherwise low-risk pregnancies, MPS was associated with higher rates of MSAF, NRFHR, undiagnosed FGR, and NICU admissions, probably mediated via placental FVM. These worrisome findings mandate patient counseling and further investigation in larger population-based studies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Abstract MP61: Evidence of Impaired Microvascular Function a Decade After Delivery in Women With Placental Malperfusion Lesions

Introduction: Maternal vascular malperfusion (MVM) lesions in the placenta are characterized by incomplete vascular remodeling and vessel features similar to atherosclerosis. MVM lesions indicate a maladaptive maternal vascular response to pregnancy, are often detected in hypertensive disorders of pregnancy (HDP), and may provide a pathologic link to future cardiovascular disease. The endothelial glycocalyx is a glycoprotein-rich layer that is critical for microvascular health and damage may have an important role in the pathophysiology of microcardiovascular disease risk. Hypothesis: We hypothesized that women with malperfusion lesions of the placenta are more likely to evidence microvascular glycocalyx derangement a decade after delivery compared to women without these lesions and that this effect would be most pronounced among women with a history of HDP. Methods: A total of 412 women with placental pathology (N=129 with MVM lesions, N=283 without MVM lesions) were evaluated at 8-10 years postpartum. Placental specimens were reviewed by a blinded perinatal pathologist . HDP (including preeclampsia and gestational hypertension) were abstracted from the medical record. Glycocalyx barrier function was assessed using sublingual sidestream dark field imaging, with reduction defined as deeper penetration of red blood cells (RBCs) into the glycocalyx of the sublingual microcirculation (5-25μm diameter). We compared the median diameter (size) of microvessels, penetration of RBCs into the glycocalyx (perfused boundary region, PBR) and microvascular density (total length of perfused microvessels/mm 2 surface area) in women with and without MVM lesions. Results: Women with placental MVM lesions had smaller-sized sublingual vessels (median 8.59 μM [IQR 8.12, 9.19] vs. 9.01 μM [IQR 8.37, 9.64]; p&lt;0.001), and a lower density of vessels compared to women without lesions. Glycocalyx perfused boundary region was unexpectedly lower in women with MVM lesions (median 2.20 μM [IQR 2.06, 2.43] vs. 2.32 μM [IQR 2.15, 2.50]; p=0.003) in 10-19 μM vessels. Women with HDP and MVM lesions appear to be the most impacted, with the smallest size vessels (median 8.47 [IQR 8.09-9.13]) and the lowest glycocalyx PBR across all vessel sizes. Women with MVM lesions without a HDP similarly had evidence of microvascular glycocalyx derangement whereas women with HDP without placental lesions had a glycocalyx profile similar to women without MVM or a history of HDP. Conclusions: A decade after delivery, women with a history of placental malperfusion lesions had alterations in microvascular perfusion. Women with MVM lesions and a history of HDP appear to be the most severely impacted, which may reflect an underlying maladaptive vascular phenotype detected in the placenta at the time of pregnancy that might provide pathologic insight into future maternal microvascular health.

Pre-conception blood pressure and evidence of placental malperfusion

BackgroundEvidence of placental maternal vascular malperfusion is associated with significant perinatal outcomes such as preeclampsia, intrauterine growth restriction and preterm birth. Elevations in pre-pregnancy blood pressure increase the risk for poor perinatal outcomes; however, the evidence linking pre-pregnancy blood pressure and placental malperfusion is sparse.Materials and methodsWe conducted a retrospective case-control study of women with singleton gestations with placental evaluations who delivered at Magee-Womens Hospital in 2012. Charts from 100 deliveries with placental malperfusion lesions (vasculopathy, advanced villous maturation, infarct, or fibrin deposition) and 102 deliveries without placental malperfusion were randomly selected for screening. Blood pressure, demographic, and clinical data were abstracted from pre-pregnancy electronic medical records and compared between women with and without subsequent placental malperfusion lesions.ResultsOverall, 48% of women had pre-pregnancy records, and these were similarly available for women with and without placental malperfusion. Women with placental malperfusion demonstrated a reduction in their pre- to early pregnancy decrease in diastolic blood pressure (DBP). Adjusted for race, pre-pregnancy BMI, age, pre-conception interval, and gestational age at the first prenatal visit, the difference in pre- to early pregnancy DBP was significantly less in women with placental malperfusion compared to those without this pathologic finding (− 1.35 mmHg drop vs − 5.6mmg, p < 0.05).ConclusionA blunted early gestation drop in DBP may be a risk factor for placental malperfusion, perhaps related to early pregnancy vascular maladaptation. The ability of the electronic medical record to provide pre-pregnancy data serves as an underutilized approach to study pre-pregnancy health.

Distinctive patterns of placental lesions in pre-eclampsia vs small-for-gestational age and their association with fetoplacental Doppler.

To describe placental histopathological findings in a large cohort of pregnancies complicated by pre-eclampsia (PE) and/or small-for-gestational age (SGA), and to investigate their association with fetoplacental Doppler parameters. This was a prospective observational study of normotensive pregnancies with SGA (defined as birth weight < 10th centile) (n = 184), PE pregnancies with a normally grown fetus (n = 102), pregnancies with both PE and SGA (n = 120) and uncomplicated pregnancies (n = 202). Uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) artery pulsatility indices (PI) were assessed. The cerebroplacental ratio (CPR) was calculated by dividing MCA-PI by UA-PI. Doppler parameters were considered abnormal when UtA-PI or UA-PI was > 95th centile or MCA-PI or CPR was < 5th centile. Placental lesions were categorized as vascular (maternal or fetal side), immunoinflammatory or other, according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Comparison between the study groups was performed using univariate and multiple regression analysis, and logistic regression was used to determine the relationship between abnormal Doppler parameters and placental lesions. Maternal-side vascular lesions were significantly more common in PE pregnancies with SGA than in the other groups (PE + SGA, 73% vs PE, 46% vs SGA, 38% vs controls, 31%; P = 0.01) and included mainly two types of lesion: developmental (PE + SGA, 13% vs PE, 5% vs SGA, 3% vs controls, 1.5%; P < 0.001) and malperfusion (PE + SGA, 70% vs PE, 39% vs SGA, 32% vs controls, 25%; P = 0.001). In contrast, the incidence of fetal-side developmental lesions was significantly higher in normotensive SGA pregnancies than in controls and PE pregnancies (PE + SGA, 0% vs PE, 3% vs SGA, 8% vs controls, 2%; P = 0.001). All cases displayed a lower prevalence of infectious lesions than did controls, with the highest prevalence of immune lesions observed in pregnancies with both PE and SGA (PE + SGA, 18% vs PE, 8% vs SGA, 10% vs controls, 9%; P = 0.001). All fetoplacental Doppler parameters evaluated were associated with maternal-side vascular lesions, mainly malperfusion (mean UtA-PI: odds ratio (OR), 2.45 (95% CI, 1.51-3.97); UA-PI: OR, 2.05 (95% CI, 1.02-4.47); MCA-PI: OR, 2.75 (95% CI, 1.40-5.42); CPR: OR, 1.75 (95% CI, 1.04-2.95)). This association was evident mainly in the normotensive SGA group, being non-significant in controls or PE pregnancies without SGA. No significant associations were observed between fetoplacental Doppler parameters and other placental lesions in any of the study groups. PE and SGA are associated with different patterns of placental histopathological lesions in accordance with the clinical manifestation of the placental disorder (maternal vs fetal). Fetoplacental Doppler findings show an association with placental malperfusion lesions on the maternal side, supporting the use of abnormal Doppler as a surrogate for placental insufficiency. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

694: Placental malperfusion lesions, excess weight gain, and adverse outcomes in women with gestational diabetes

694: Placental malperfusion lesions, excess weight gain, and adverse outcomes in women with gestational diabetes