Uteroplacental Vascular Pathology Research Articles

Placental Pathology and Maternal Risk Factors for Stillbirth: A Case-Control Study.

Background Fetal death is the delivery of a fetus with no sign of life, as indicated by the absence of breathing, heartbeat, pulsation of the umbilical cord, or definite movement of voluntary muscles. Nearly 2.6 million stillbirths are estimated to occur worldwide every year. Almost all of these (98%) stillbirths occur in low- and middle-income countries. About one-sixth of the stillbirths globally were recorded in India in 2019, making it the most burdened country in the world. In light of this, we conducted a study to identify the placental pathologies and maternal factors associated with stillbirth. Methodology A case-control study was conducted at the Department of Obstetrics & Gynecology, Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), from June 2022 to May 2023. Cases included pregnant women with a gestational age of 28 weeks or more who delivered a stillbirth infant at VIMSAR, and controls included gestational age-matched deliveries with live birth. Consent to participate in the study was obtained before enrolment. The final sample size was 79 cases and controls. The chi-square test was performed for bivariate analysis, and logistic regression was used for multivariate analysis. Results In our study, we found a significant association between maternal age of more than 30 years (odds ratio (OR) = 3.01, 95% confidence interval (CI) = 1.91-4.22, p = 0.012), maternal education (with up to the primary level or less: OR = 6.19, 95% CI = 2.92-7.87, p = 0.012), history of addiction (tobacco chewing: OR = 5.58, 95% CI = 3.71-7.11, p = 0.03), and the number of antenatal visits (no visit: OR = 6.87, 95% CI = 2.91-7.79, p = 0.019) with an increased risk of stillbirth. Among the obstetrical complications, pre-eclampsia/eclampsia (OR = 3.87, 95% CI = 1.98-5.11, p = 0.001), premature rupture of membranes (PROM)/preterm premature rupture of the membranes (PPROM) (OR = 2.49, 95% CI = 1.31-3.91, p = 0.03) and antepartum hemorrhage (APH) (OR = 2.66, 95% CI = 1.65-3.58, p = 0.02) were found to be significantly related with stillbirth. Among placental pathologies, uteroplacental vascular pathology (OR = 7.39, 95% CI = 3.01-8.97), acute chorioamnionitis (OR = 3.35, 95% CI = 2.11-5.21), chronic inflammation (OR = 2.33, 95% CI = 1.91 4.17), calcific changes (OR = 4.46, 95% CI = 2.56-6.01), and retroplacental clots (OR = 9.95, 95% CI = 4.39-11.71) were associated with stillbirth. Conclusions In our study, advanced maternal age, absence of antenatal visits, low level of education, tobacco addiction, pre-eclampsia/eclampsia, APH, and PROM in pregnancy were the major risk factors associated with stillbirth. Uteroplacental vascular pathology, chorioamnionitis, chronic inflammation, retroplacental hematoma, and calcific changes were the most significant placental lesions associated with stillbirth.

Placental pathology and maternal factors associated with stillbirth: An institutional based case-control study in Northern Tanzania.

ObjectiveTo determine the placental pathologies and maternal factors associated with stillbirth at Kilimanjaro Christian Medical Centre, a tertiary referral hospital in Northern Tanzania.MethodsA 1:2 unmatched case-control study was carried out among deliveries over an 8-month period. Stillbirths were a case group and live births were the control group. Respective placentas of the newborns from both groups were histopathologically analyzed. Maternal information was collected via chart review. Mean and standard deviation were used to summarize the numerical variables while frequency and percentage were used to summarize categorical variables. Crude and adjusted logistic regressions were done to test the association between each variable and the risk of stillbirth.ResultsA total of 2305 women delivered during the study period. Their mean age was 30 ± 5.9 years. Of all deliveries, 2207 (95.8%) were live births while 98 (4.2%) were stillbirths. Of these, 96 stillbirths (cases) and 192 live births (controls) were enrolled. The average gestational age for the enrolled cases was 33.8 ±3.2 weeks while that of the controls was 36.3±3.6 weeks, (p-value 0.244). Of all stillbirths, nearly two thirds 61(63.5%) were males while the females were 35(36.5%). Of the stillbirth, 41were fresh stillbirths while 55 were macerated. The risk of stillbirth was significantly associated with lower maternal education [aOR (95% CI): 5.22(2.01–13.58)], history of stillbirth [aOR (95%CI): 3.17(1.20–8.36)], lower number of antenatal visits [aOR (95%CI): 6.68(2.71–16.48), pre/eclampsia [aOR (95%CI): 4.06(2.03–8.13)], and ante partum haemorrhage [OR (95%CI): 2.39(1.04–5.53)]. Placental pathology associated with stillbirth included utero-placental vascular pathology and acute chorioamnionitis.ConclusionsEducating the mothers on the importance of regular antenatal clinic attendance, monitoring and managing maternal conditions during antenatal periods should be emphasized. Placentas from stillbirths should be histo-pathologically evaluated to better understand the possible aetiology of stillbirths.

Sex of the Fetus can be Associated with Placental Pathologies in Premature Deliveries

Background: There are many pregnancy complications that are significantly associated with the gender of the fetus; one of them is preterm labour, which is an important obstetric problem that may lead to many perinatal morbidity and mortality. Objective: To find out whether there is a relation between the findings of placental pathology of premature deliveries and gender difference. Patients and Methods: Fifty deliveries before a 32 week gestational age. Obstetrical, and placental histological findings have been compared among all males (n=25), and females (n=25) premature neonates. Results: The male premature fetus had distribution rate in maternal age, gestation age at the time of delivery, placental weight, and feto-placental weight-ratio in females, but a higher birth-weight centile ([55.09±11.3] versus [43.09±8.2]). Histopathology of the placenta found no significant association of fetal-sex with acute inflammatory lesions (p=0.09), intra-placental vascular pathological findings, or utero-placental vascular pathology. However, the chronic inflammatory lesion showed a higher pathological score in male fetuses than in the females (p=0.01). Conclusion: Premature deliveries with less than thirty-two weeks, the male fetal-sex had higher placental pathological lesions, suggesting maternal immunological responses towards the invading trophoblasts. The immunological background of these pathological lesions needs further studies. Keywords: Male fetal sex, placental pathology, premature delivery

OP 33 Correlation between uterine artery Doppler parameters and sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders

Introduction The underlying pathology of hypertensive pregnancy disorders is a failure in trophoblast invasion and spiral artery remodeling. This leads to a misbalanced release of antiangiogenic sFlt-1 and angiogenic PlGF placental factors and to a high resistance and low compliance to uterine artery blood flow. Consequently, in hypertensive pregnancy disorders, sFlt-1/PlGF ratio and uteroplacental impedance are increased. Objective To explore correlations between sFlt-1/PlGF ratio and uterine artery Doppler parameters in pregnancies complicated by different types of hypertensive pregnancy disorders. Patients and methods We performed prospective observational study to derive and calculate sFlt-1/PlGF ratio and to measure uterine artery resistance index (RI-AtU) and pulsatility index (PI-AtU) in singleton pregnancies in whom preeclampsia (PE), preeclampsia with intrauterine growth retardation (PE (+IUGR)), or intrauterine growth retardation (IUGR) was suspected on admittance after 24 weeks 0 days. For statistical analyses, we used multiple comparisons (Bonferroni test) and Sperman’s rho. Results Demographic and clinical characteristics are presented in Fig. 1. Values for sFlt-1/PlGF ratio, RI-AtU and PI-AtU are presented in Fig. 2. Log values of sFlt-1/PlGF ratio were not significantly different among groups. Average RI-AtU and PI-AtU were significantly higher in PE(+IUGR) compared to PE (p = 0.28; p = 0.05; respectively) but were not significantly different between IUGR and PE, or IUGR and PE (+IUGR). In PE, RI-AtU and PI-AtU were significantly positively correlated with sFlt-1/PlGF ratio (p = 0.01; p = 0.050; respectively). In IUGR, only RI-AtU was significantly positively correlated with sFlt-1/PlGF ratio (p = 0.041). In PE (+IUGR), neither RI-AtU nor PI-AtU were correlated with sFlt-1/PlGF ratio. Conclusion Differences in correlations between sFlt-1/PlGF ratio and uterine artery Doppler parameters suggest that PE might be a decompensation phase of beforehand healthy cardiovascular system due to uteroplacental vascular pathology. However, PE (+IUGR) and IUGR might be a consequence of various degrees of preexisting systemic cardiovascular pathology which might lead to various degrees of uteroplacental pathology. Download : Download high-res image (367KB) Download : Download full-size image Download : Download high-res image (349KB) Download : Download full-size image

The impact of maternal BMI, parity and GA on the comparative efficacy of transcervical foley catheter with or without an extraamniotic saline infusion for cervical ripening and labor induction in women with an unfavorable cervix

TERM BIRTH MICHAEL RUMA, AMY HERRING, CAROLYN SALAFIA, JOHN THORP, University of North Carolina at Chapel Hill, Obstetrics & Gynecology, Chapel Hill, North Carolina, University of North Carolina at Chapel Hill, Biostatistics, Chapel Hill, North Carolina, Columbia University Mailman School of Public Health, Epidemiology, New York, New York OBJECTIVE: To assess the relationship between uteroplacental vascular histopathology and preterm birth (PTB). STUDY DESIGN: Placentas from the prospective Pregnancy, Infection, and Nutrition study were evaluated by gross and microscopic examination by a single perinatal pathologist. Presence of uteroplacental vascular pathology, such as syncytial knots, vascular fibrosis, and thrombi were quantified. PTB was defined as delivery !37 weeks; extreme PTB was defined as !32 weeks. The relationship between uteroplacental vascular pathology and PTB was determined by Fisher’s exact or Chi-square tests. Odds ratios (OR, 95% CI) for PTB stratified by gestational age at delivery were calculated. RESULTS: Placentas from 154 PTB (78 spontaneous and 76 medically indicated) and 843 term births were analyzed. There were 21 extreme PTB. 69 (45%) of 154 PTB and 19 (90%) of extreme PTB had uteroplacental vascular pathology. Uteroplacental vascular pathology was more common among spontaneous versus medically indicated PTB (53 vs. 37%, p=.05). Uteroplacental vascular pathology was more common in extreme PTB, compared to 32-37 week PTB, and term birth (90 vs. 38, and vs. 28% respectively, p!.0001). The odds for PTB were higher among women with uteroplacental vascular pathology (Table). CONCLUSION: Uteroplacental vascular pathology is more common among PTB and extreme PTB. Understanding the etiology of uteroplacental vascular pathology may lead to a novel approach to PTB prevention.

Uteroplacental vascular pathology is associated with extreme preterm birth

Uteroplacental vascular pathology is associated with extreme preterm birth

Morphometry of the Basal Plate Superficial Uteroplacental Vasculature in Normal Midtrimester and at Term

Uteroplacental (UP) vascular arterial pathology has been associated with pregnancy complications. UP arterial structure has been characterized in placental bed biopsies, at the decidual-myometrial junction. Basal plate UP arteries, which are delivered with the placenta and thus routinely available, are not well characterized. We compared basal plate UP arterial segment morphometry in cases of elective termination of a clinically normal pregnancy at 11 to 24 weeks and of term birth. This study was done in a community-based obstetric service in New York City. UP arteries were identified in placentas of 20 midtrimester (MT) cases and 17 term (TERM) cases. We measured 336 UP artery cross-sections from 46 TERM and 290 MT cases. The basal plate UP artery path length was calculated as the distance between (x,y) coordinates of estimated centers of lumen cross-sections. Basal plate thickness near UP arteries, UP artery cross-sectional areas, vascular luminal eccentricity, and radial standard deviation were directly measured off digital images. Nonparametric and parametric methods compared groups, with P < 0.05 considered statistically significant. In TERM cases, the basal plate thickness near UP arteries was 1.8-fold thinner (P = 0.002) and mean basal plate path lengths were 2.13-fold shorter (P < 0.0001) than in MT cases. Mean TERM UP artery cross-sectional area was 3.15-fold larger, the major axis was 1.95-fold larger, and the minor axis was 1.75-fold larger than in MT arteries (P = 0.001 to 0.008). Our data demonstrate that basal plate UP arteries (delivered with the placenta) are less tortuous, with shorter path lengths and larger areas as gestation advances. Normative morphometric data may allow improved diagnostics of placentas from complicated pregnancies.

Histologic placental lesions in women with recurrent preterm delivery

The aim of this study was to evaluate whether particular placental histopathology lesions are associated with recurrent preterm birth. We analyzed a database of 413 consecutive singleton pregnancies delivered at <32 weeks with past reproductive history available. After the exclusion of nulliparous women, the pregnancies were divided according to the obstetrical history into group 1 (n = 328), women without prior preterm delivery (PTD); group 2 (n = 49), women with one prior preterm childbirth; and group 3 (n = 36), women with > or =2 prior preterm deliveries. Demographic and clinical variables were compared among the three groups by using Kruskal-Wallis test and chi-square test for trend. Finally, the individual placental lesions (i.e. 42 lesions of acute or chronic inflammation, uteroplacental vascular pathology, and intraplacental villous lesions) were correlated with the number of prior preterm deliveries by using regression analysis. A two-tailed P < 0.05 was considered significant. No differences were found among the three groups in demographic or clinical variables. Regression analysis of scored placental lesions corrected for gestational age at delivery showed that the number of prior preterm deliveries was correlated only with chronic marginating choriodeciduitis (correlation coefficient = 0.13; P = 0.01) and acute choriodeciduitis (correlation coefficient = 0.14; P = 0.008). Among women delivered at <32 weeks, those with prior preterm birth have histologic findings compatible with acute or chronic inflammatory involvement of the uterine cavity, suggesting that a prepregnancy endometrial infection rather than an ascending intrapregnancy pathway may be responsible for some recurrences of PTD.

Gender differences of placental dysfunction in severe prematurity

Rates of several obstetric complications have been reported to vary with fetal gender. We investigated whether a sex difference exists in findings at placental histology of extreme prematurity. Case-control study. University Hospital. Four hundred and thirty-seven consecutive deliveries before 32 weeks of gestation of singleton, liveborn, non-anomalous infants. Obstetric, neonatal and placental histologic findings were compared between male (n= 232) and female (n= 205) neonates. Histologic evidence of acute placental inflammation, uteroplacental vascular pathology, intraplacental vascular pathology and chronic placental inflammation. Male fetuses had similar racial distributions, rate of nulliparity, maternal age, gestational age at delivery, placental weight and fetoplacental weight ratio as female fetuses, but higher birthweight centiles (41 [27] vs 33 [26]). Placental histology showed no association between fetal gender and lesions of acute inflammation (P= 0.08), intraplacental vascular pathology (P= 0.16) or uteroplacental vascular pathology (P= 0.83). However, lesions of chronic inflammation had a significantly higher score in male than in female fetuses (P= 0.001). When we examined the distribution of chronic placental inflammation, significantly more severe lesions were noted in male than in female fetuses at the implantation site (i.e. the area of interstitial trophoblast invasion of the maternal decidua and maternal endovascular trophoblast remodelling), than within the placental villi (chronic villitis) or in the amniochorionic membranes (where interstitial trophoblast invasion is minimal). In premature deliveries at <32 weeks, male fetal gender is associated with placental lesions suggestive of a maternal immune response against the invading interstitial trophoblast. The immunologic basis of these findings deserves further studies.

Pathology findings in preterm placentas of women with autoantibodies: a case–control study

Objective: To evaluate the placental histopathology findings in women with systemic lupus erythematosus or antiphospholipid syndrome delivered preterm.Methods: We performed a case-controlstudy comparing clinical outcomes and placental histopathology of 18 consecutive singleton pregnancies with systemic lupus erythematosus (n = 9) or antiphospholipid syndrome (n = 9) deliveredbetween 24 and 37 weeks, and 54 controls matched for gestational age and type of preterm delivery (spontaneous or indicated). Placental examinations were performed by a single pathologist, and placentallesions were grouped into four categories: uteroplacental vascular pathology and related villous lesions; coagulation-related damage; chronic inflammation; and acute inflammatory lesions. Statistical analysisincluded the Mantel-Haenzsel or Fisher's exact test, and logistic regression, with a value of p < 0.05 or an odds ratio (OR) with 95% confidence intervals (CI) not inclusive of unity consideredsignificant.Results: Lupus anticoagulant was positive in ten out of 18 cases and medium or high positive IgG anticardiolipin antibodies in seven out of 18. Antenatal treatment included corticosteroids(n = 9), low-dose aspirin (n = 15) and heparin (n = 8). Rates of necrotizing enterocolitis (33% vs. 0%, p < 0.001) and of perinatal mortality (33% vs. 9%, p = 0.02)were significantly different between cases and controls, and rates of birth weight < 10th centile approached statistical significance. Uteroplacental vascular lesions (OR 3.7, 95% CI 1.1, 11.7) and coagulation-relateddamage (OR 16.8, 95% CI 3.9, 72.6) were significantly more common among cases than controls, and rates of chronic inflammatory lesions approached significance.Conclusions: Cases of systemiclupus erythematosus and antiphospholipid syndrome delivered preterm are associated with a significant increase in placental vascular and coagulation-related lesions, which are reflected clinically by higherrates of perinatal mortality, necrotizing enterocolitis, and small-for-gestational age neonates.

Uterine Artery Doppler Flow and Uteroplacental Vascular Pathology in Normal Pregnancies and Pregnancies Complicated by Pre-eclampsia and Small for Gestational Age Fetuses

This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and/or small for gestational age (SGA) fetuses and 27 women with normal pregnancies undergoing elective caesarean section were included. We obtained uterine artery Doppler waveforms at a mean of 4 days before delivery. Placental bed biopsies were obtained at caesarean section and analysed for physiological changes and pathological changes.We found that abnormal uterine artery Doppler flow was strongly associated with pregnancy complications. Absence of physiological changes was seen in 58 per cent of complicated pregnancies and 40 per cent of normal pregnancies. Pathological changes were seen in 58 per cent of complicated pregnancies and 53 per cent of normal pregnancies; they occurred in spiral arteries with and without physiological changes, and there was no significant correlation to Doppler results. In conclusion, absence of physiological changes is associated with abnormal uterine artery Doppler flow and pregnancy complications. However, there is a gradient in the severity of uteroplacental vascular pathology and the correlation with pregnancy complications is not as strong as previously thought. There is also a significant degree of uteroplacental vascular pathology in normal pregnancies with normal uterine artery Doppler flow. This variation may be partly due to sampling error, as a typical biopsy contains only one or two spiral arteries. We hypothesize that additional factors might be necessary to induce the clinical syndrome of pre-eclampsia.

Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses

Objective To identify placental histopathology associated with absent and reversed end-diastolic flow demonstrated by umbilical artery (UA) Doppler velocimetry in fetal growth restriction (FGR). Methods Between January 1989 and June 1995, 64 consecutive, nonanomalous singletons at less than the tenth percentile for birth weight were admitted to the neonatal intensive care unit, with UA Doppler velocimetry obtained within 3 days of delivery; 54 of the 64 (84%) had placental histopathology. Umbilical artery Doppler wave forms were classified as having end-diastolic flow ( n = 26), and either absent ( n = 20) or reversed end-diastolic flow ( n = 8). Blinded review of placental histology scored lesions in categories of intraplacental vaso-occlusion, uteroplacental vascular pathology, chronic inflammation, and coagulation. Results Using cases of FGR with end-diastolic flow present as the control population, we found that absent end-diastolic flow cases had significantly more fetal stem vessels with medial hyperplasia and luminal obliteration, and cases of reversed end-diastolic flow had significantly more poorly vascularized terminal villi, villous stromal hemorrhage, “hemorrhagic endovasculitis,” and abnormally thin-walled fetal stem vessels (each P Conclusion In FGR, UA Doppler velocity wave forms do not demonstrate a continuum of placental lesions in which reversed end-diastolic flow reflects more severe placental histopathology than absent end-diastolic flow and enddiastolic flow present. As expected, absent end-diastolic flow cases had more occlusive lesions of the intraplacental vasculature. In reversed end-diastolic flow, lesions suggesting vascular remodeling and/or damage by pathologic conditions of intraplacental flow predominated.

Gestational Age-Dependent Extravillous Cytotrophoblast Osteopontin(OPN) Immunolocalization in the Basal Plate and Uteroplacental Vasculature Differentiates between Normal and Growth-Restricted Fetuses † 261

Human placentation requires modulation of proliferative cytotrophoblasts to an invasive phenotype to create the intervillous space. Preeclampsia is characterized by failed trophoblast invasion and remodeling of the maternal spiral arteries. OPN is a secreted extracellular matrix protein found in many tissues including human trophoblast, and has been implicated in cell adhesion, invasion, spreading, and migration. To investigate gestational age-specific expression of OPN, immunohistochemical staining of post-partum placental tissue from 13 healthy women was performed using a monoclonal antibody against OPN (MPIIIB10-1). OPN protein was localized to the cytoplasm of invasive extravillous trophoblast from 24-28 wks (N=7). After 28 wks (N=6), OPN was undetectable in the extravillous trophoblast, and was not identified in non-invasive intravillous cytotrophoblast and syncytiotrophoblast at any gestational age (N=13). To investigate the role of OPN in uteroplacental vascular pathology, immunohistochemical staining of post-partum placentas from pregnancies complicated by preeclampsia (N=6) or intrauterine growth retardation (N=2) was performed using MPIIIB10-1 and compared to staining of placentas from gestational age-matched controls without pregnancy-induced maternal vascular disease (N=13). In the preecclampsia group, there was prominent proliferation of cytotrophoblast in the basal plate with intense OPN staining, in association with morphologic evidence of compromised uteroplacental perfusion. This staining pattern was identified in all preeclamptic placentas at 24-40 wks. In contrast, the normal and IUGR placentas did not display prominent cytotrophoblast proliferation or evidence of decreased uteroplacental perfusion: OPN staining was limited to the invasive extravillous cytotrophoblast and detected only until 28 wks. The data suggests a role for OPN in trophoblast invasion of the maternal vasculature and extracellular matrix during normal placentation, where OPN may serve as a marker for uteroplacental vascular remodeling in the human fetus. In the preeclamptic pregnancy, extravillous cytotrophoblast continues to express OPN even at advanced gestational ages, which supports the speculation that intervillous fibrin/fibrinoid may be actively involved in the remodeling of the intervillous space. OPN may be critical in this process, the successful maintenance of which may necessary for fetal compensation.

Uteroplacental pathology and maternal arterial mean blood pressure in spontaneous prematurity.

To examine if maternal blood pressure is directly related to the presence and severity of uteroplacental vascular pathology in nonpreeclamptic preterm birth. A set of consecutive nonanomalous singleton live births delivered at 22-32 weeks (excluding maternal diabetes mellitus and chronic hypertension) between 1989 and 1994 included 342 cases of spontaneous prematurity (spontaneous premature membrane rupture [PROM], preterm labor with intact membranes [PTL], and nonhypertensive abruption) with mean arterial blood pressure at admission available in the maternal record. Presence and extent of placental lesions were scored. Mean maternal arterial blood pressure on admission was significantly related to the presence/extent of uteroplacental vascular lesions (P = .01) and to lesions of intraplacental vaso-occlusion (P = .04). These associations were independent of maternal age and gestational age at delivery. Moreover, the summation of uteroplacental and intraplacental vascular lesions into a cumulative placental vascular pathology score was even more significantly correlated with increasing mean blood pressure at admission, suggestive of synergism between these two placental pathologic processes. In nonpreeclamptic prematurity, mean maternal admission blood pressure is directly related to the severity of placental vascular pathology.

Osteopontin (OPN) immunolocalization in human cytotrophoblast differentiates between normal and growth-restricted fetuses in the context of uteroplacental vascular pathology

Osteopontin (OPN) immunolocalization in human cytotrophoblast differentiates between normal and growth-restricted fetuses in the context of uteroplacental vascular pathology

Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses

To identify placental histopathology associated with absent and reversed end-diastolic flow demonstrated by umbilical artery (UA) Doppler velocimetry in fetal growth restriction (FGR). Between January 1989 and June 1995, 64 consecutive, nonanomalous singletons at less than the tenth percentile for birth weight were admitted to the neonatal intensive care unit, with UA Doppler velocimetry obtained within 3 days of delivery; 54 of the 64 (84%) had placental histopathology. Umbilical artery Doppler wave forms were classified as having end-diastolic flow (n = 26), and either absent (n = 20) or reversed end-diastolic flow (n = 8). Blinded review of placental histology scored lesions in categories of intraplacental vaso-occlusion, uteroplacental vascular pathology, chronic inflammation, and coagulation. Using cases of FGR with end-diastolic flow present as the control population, we found that absent end-diastolic flow cases had significantly more fetal stem vessels with medial hyperplasia and luminal obliteration, and cases of reversed end-diastolic flow had significantly more poorly vascularized terminal villi, villous stromal hemorrhage, "hemorrhagic endovasculitis," and abnormally thin-walled fetal stem vessels (each P < .005). In FGR, UA Doppler velocity wave forms do not demonstrate a continuum of placental lesions in which reversed end-diastolic flow reflects more severe placental histopathology than absent end-diastolic flow and end-diastolic flow present. As expected, absent end-diastolic flow cases had more occlusive lesions of the intraplacental vasculature. In reversed end-diastolic flow, lesions suggesting vascular remodeling and/or damage by pathologic conditions of intraplacental flow predominated.