Maternal Vascular Lesions Research Articles

Placental pathology of IVF-conceived dichorionic diamniotic twins after fresh embryo versus frozen-thawed transfer

IntroductionTo compare histopathological findings of placentas of dichorionic diamniotic twin pregnancies of in-vitro fertilization (IVF), conceived after fresh embryo transfer (ET) and frozen-thawed ET. MethodsThis retrospective study compared dichorionic diamniotic twin IVF pregnancies that resulted in livebirths during 2010-2022. The placental findings were classified according to definitions curated by the 2016 Amsterdam Placental Workshop Group Consensus Statement. A multivariate logistic analysis was constructed to estimate the odds ratios (OR) of placental histopathology abnormal findings, adjusted for maternal age, body mass index and nulliparity. ResultsThe mean gestational age at birth was lower following fresh ET pregnancies (n=236) than frozen-thawed ET pregnancies (n=122) (34.89 vs 35.77 weeks, p=0.003). For the fresh ET compared to the frozen-thawed ET group, rates were higher of preterm birth (69.5% vs. 55.7%, p=0.011), low birthweight (71.6% vs 57.4%, p<0.001) and very low birthweight (14.2% vs 9.0%, p value one sided=0.029). For the fresh ET compared with the frozen-thawed ET group, the rates were higher of maternal vascular lesions (20.3% vs. 11.5%, p=0.003), placental hemorrhage (12.7% vs. 7%, p=0.021), and villous lesions related to maternal vascular lesions (7.2% vs. 3.7%, p value one sided=0.04). A multivariate logistic analysis showed a higher risk of maternal or neonatal vascular lesions for twin pregnancies after fresh ET than frozen-thawed ET (adjusted OR=1.91, 95% CI 1.26-2.92, p=0.011). ConclusionsFollowing fresh ET compared to frozen-thawed ET, obstetrical and neonatal outcomes were worse, and the risk of maternal vascular lesions was greater.

Insights into Placental Pathology: Analyzing Patterns and Fetal Outcomes in 205 Livebirths at Bugando Medical Centre, Mwanza, Tanzania

Background: The placenta facilitates vital nutrient exchange between fetus and mother, offering insights into fetal and maternal health. Despite its significance, research on placental histopathology in Tanzania is scarce. This study investigates placental features, maternal factors, and their impact on fetal outcomes at Bugando Medical Centre from January to May 2022. Methods: This 5-month cohort study included 205 mothers delivering at BMC. Fetal outcomes were evaluated at birth and after seven days, with maternal characteristics recorded at delivery. Participants were from the twenty-eighth week of gestation, excluding those with intrauterine fetal death or multiple pregnancies. Data on placental histology, maternal factors, and fetal outcomes were collected systematically, while statistical analysis employed STATA version 15, utilizing descriptive statistics. Results: In this study of 205 placentas, participants had a median age of 29 years and a mean gestational age of 38 weeks. Histopathological patterns were present in 61% of placentas, with acute inflammation (22%) and maternal vascular malperfusion (20.8%) being most common. Favorable outcomes were observed in 81% of newborns, while 19% experienced poor outcomes, including 1.9% early neonatal deaths. Most placental lesions were mild (53.6%), with severe pathology in 2.9% of cases. Acute inflammation correlated with various admission reasons, especially neonatal sepsis (60%). Maternal vascular lesions were associated with prematurity (63.6%) and birth asphyxia (40%). Chronic inflammation was more prevalent among low-birth-weight infants (18.8%), while very low birth weight was common in cases of maternal vascular lesions (68.8%). Conclusion: The majority of placentas showed normal or mild pathology, associated with positive fetal outcomes. Further research is needed to understand placental changes and their impact on maternal-fetal health.

Evaluation of placental pathologies in cases of placenta previa

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

Maternal Vascular Lesions in the Placenta Predict Vascular Impairments a Decade After Delivery.

Women with adverse pregnancy outcomes later experience excess hypertension and cardiovascular disease, but how the events are linked is unknown. Examination of the placenta may provide clues to vascular impairments after delivery. Maternal vascular malperfusion lesions (MVMs) were abstracted from clinical reports, validated and characterized using clinical guidelines and severity score. A total of 492 women (170 with MVMs and 322 without MVMs) participated in a study visit 8 to 10 years after delivery to assess blood pressure, cardiometabolic factors, and sublingual microvascular features using sidestream dark field imaging. Covariates included age, race, adverse pregnancy outcomes (preeclampsia, small for gestational age, and preterm birth), and health behaviors. Women with versus without MVM had a distinct sublingual microvascular profile comprised of (1) lower microvascular density (-410 μm/mm2, P=0.015), (2) higher red blood cell filling as a marker of perfusion (2%, P=0.004), and (3) smaller perfused boundary region (-0.07 µm, P=0.025) as a measure of glycocalyx integrity, adjusted for covariates including adverse pregnancy outcomes. Women with MVM also had higher adjusted diastolic blood pressure (+2.6 mm Hg, P=0.021), total and LDL (low-density lipoprotein)-cholesterol (+11.2 mg/dL, P=0.016; +8.7 mg/dL, P=0.031). MVM associations with subsequent cardiovascular measures did not vary by type of adverse pregnancy outcome, except among women with preterm births where blood pressure was higher only among those with MVM. Results were similar when evaluated as MVM severity. A decade after delivery, women with placental vascular lesions had an adverse cardiovascular profile comprised of microvascular rarefaction, higher blood pressure and more atherogenic lipids. Placental histopathology may reveal a woman's early trajectory toward subsequent vascular disease.

Unfolding the pathophysiology of congenital thrombotic thrombocytopenic purpura in pregnancy: lessons from a cluster of familial cases

Thrombotic thrombocytopenic purpura (TTP), a rare, potentially life-threatening thrombotic microangiopathy, manifests either as congenital TTP or acquired forms. It is caused by the absence or severe depletion of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) protease, leading to the accumulation of ultra large von Willebrand factor multimers as well as extensive platelet adhesion and clumping, which can ultimately cause severe secondary end-organ damage. Pregnancy can provoke or exacerbate TTP, leading to maternal and fetal complications. In this report, we focused on pregnancy outcomes in a recently recognized cohort of congenital TTP patients of Bedouin Arab descent in southern Israel who were all homozygous for a novel c.3772delA variant of the ADAMTS13 gene, leading to the clinical manifestations of TTP largely during pregnancy. All patients presented in this study belong to 2 closely related families of Arab Bedouin descent and were found to be homozygous for a novel ADAMTS13-c.3772delA variant. The cohort consisted of 19 females; 16 of them had congenital TTP and had been pregnant and were thus included. Patient data were collected from electronic medical records. Of note, 13 women from our cohort, who delivered 14 fetuses (owing to 1 twin pregnancy), were diagnosed with congenital TTP following complicated pregnancies, which included recurrent pregnancy loss, stillbirth, early onset preeclampsia (both mild and severe), hemolysis, elevated liver enzymes and low platelet count syndrome, intrauterine growth restriction with abnormal Doppler flow, preterm premature rupture of membranes, and a total perinatal mortality rate of 30.7% (4/13). An additional 3 women, who were diagnosed owing to complications outside of pregnancy and at older ages, experienced TTP during their pregnancies, which occurred before diagnosis. Subsequent pregnancies were treated with fresh frozen plasma leading to a 100% fetal survival rate in the pregnancies that reached fetal viability. All placentas had lesions consistent with maternal vascular underperfusion. However, the severity and frequency of these lesions were lower in the 8 placentas from pregnancies treated with fresh frozen plasma. This case series details a distinctive cohort of congenital TTP patients, all homozygous for the same, novel ADAMTS13 variant, who presented with clinical complications during pregnancy and maternal vascular lesions of underperfusion in the placenta. Our findings imply that the variant identified in the ADAMTS13 gene in our cohort may have a specific functional impact on the placenta, and that treatment with fresh frozen plasma during pregnancy ameliorates the course of the disease, leading to a milder phenotype or a normal pregnancy in the majority of cases.

462 Postpartum antihypertensive treatment in preeclamptic patients – correlation to clinical and placental findings

We aimed to examine if clinical and placental findings in preeclampsia (PET) can predict the need for anti-hypertensive treatment in the postpartum. This was a retrospective cohort of live singleton deliveries at 24.0 – 42.0 weeks gestation complicated by PET. Included were deliveries, we excluded patients with chronic hypertension and anti-hypertensive treatment during pregnancy. Obstetric outcomes and placental pathology reports were compared between patients who required antihypertensive treatment during the postpartum period (treatment group) and patients who did not (no treatment group). A total of 276 deliveries with a diagnosis of PET were analyzed – 90 in the treatment group and 186 in the no treatment group. There were no differences between the groups regarding demographics and previous PET. Significantly more patient in the treatment group delivered prematurely - 61.1% vs. 34.9%, p<0.001. The rate of severe preeclampsia was significantly higher in the treatment group - 91.1% vs 56.9%, respectively, p<0.001, and a higher rate of cesarean delivery was also noted in this group - 84.4% vs. 63.9%, p<0.001. On placental examination, a higher rate of marginal and retroplacental hematomas was noted in the treatment group (p=0.02), as was a trend for more maternal vascular lesions (p=0.05). In a logistic regression analysis, gestational age (OR 0.87, 95% CI 0.80-0.94, p=0.001) and severe PET (OR 7.26, 95% CI 3.20-16.47, p<0.001) were found independently correlated to post-partum treatment. In separate regression analysis among patients treated while hospitalized, nulliparity (OR 0.49, 95%CI 0.25-0.98, p=0.04) was also found significantly correlated with treatment at discharge. Antihypertensive treatment in the postpartum correlates to PET severity and gestational age, while nulliparous patients are also likely to require treatment after discharge

Is advanced maternal age associated with placental vascular malperfusion? A prospective study from a single tertiary center.

Pregnancy at advanced maternal age (AMA) has become more common. There has been concern regarding the adverse effect deferring pregnancy might have on pregnancy outcomes. We aimed to prospectively study the effect of AMA on placental pathology. A prospective case-control study was performed in a single university center. Placental histopathology, maternal demographics, labor characteristics, and neonatal outcomes of pregnancies with AMA were collected and compared to matched controls. We defined AMA as maternal age > 35years at delivery. In attempt to isolate the effect of maternal age, we excluded cases complicated by preterm birth, hypertensive disorders, diabetes mellitus, small for gestational age, and congenital/genetic anomalies. The study group included 110 AMA patients that were matched with controls. The groups did not differ in maternal demographics, but the AMA group had a higher rate of assisted reproductive technologies (ART) as compared to the control group (p < 0.001). Placentas in the AMA group were characterized by a higher rate of maternal vascular lesions (MVM) (39.1% vs. 24.5%, p = 0.003), but not fetal vascular malperfusion lesions (p = 0.576). In multivariable analysis maternal age was associated with placental MVM lesions independent of all other maternal demographics (aOR 1.18 95% CI 1.06-3.17). Neonatal outcomes did not significantly differ between the groups. After excluding all background morbidities-AMA was associated with a higher rate of placental MVM lesions vs. controls. These findings suggest an independent effect of AMA on placental function. Large prospective trials are needed to study the clinical importance of these findings.

Abstract MP65: Maternal Vascular Lesions in the Placenta May Identify Women Susceptible to Masked Hypertension a Decade After Pregnancy

Introduction: Women with placentally mediated pregnancy complications such as preeclampsia have excess hypertension and cardiovascular disease later in life, but the underlying pathophysiology linking these conditions is unknown. Hypothesis: We considered that histological examination of the placenta may reveal maternal vascular impairments that identify a group susceptible to blood pressure (BP) elevations a decade after delivery, including elevations that may only be detectable using out of office BP measurement. Method: Women with a singleton live birth at Magee-Womens Hospital (Pittsburgh, PA) during 2008-2009 were enrolled 8-10 years after delivery (n=248). Pregnancy features and placental pathology were abstracted from medical records. Women with placental vasculopathy (several related lesions arising from impaired remodeling of maternal myometrial and decidual arteries, n=24) or infarcts (n=32) were compared to women with neither lesion (n=192). Clinic BP was measured three times by trained research staff using a standard protocol and a validated home BP device. Women were trained to measure their BP twice daily for 7 days using the same device mentioned above. Subsequently, time and date stamped BP measures were downloaded (mean 12.2 measures ± 4.5). BP status (elevated, stage 1, stage 2) was identified using the 2018 ACC/AHA guidelines for clinic and home BP measures. Sustained normotensive, white coat, masked, and sustained hypertension status were classified. Results: Women were, on average, 37 years of age at measurement. In analysis controlled for age and race (p-value &lt; 0.05) those with placental vasculopathy had higher mean diastolic BP in clinic and at home (80.5 ± 13.3 mmHg, 79.9 ± 10.4, respectively) than women without vascular lesions in the placenta (75.4 ± 9.8 mmHg and 74.3 ±8.6, respectively). In addition, women with placental vasculopathy had a higher prevalence of masked hypertension (higher elevated BP status measured at home vs. in clinic; 37.5% vs. 14.1%) that persisted after accounting for maternal age and race (adjusted OR 4.7, 95% confidence interval 1.6, 13.8). Vasculopathy associations were similar after excluding women with preeclampsia (n=42), the pregnancy complication most strongly associated with placental vascular pathology. There were modest, non-significant associations between placental infarcts and all measures of maternal blood pressure. Conclusions: Irrespective of prior preecclampsia, women with placental evidence of vasculopathy have excess hypertension and particularly masked hypertension in the decade after pregnancy. Our results emphasize the value of out of office blood pressure measurement, and indicate that placental vasculopathy may be pathophysiologically related to development of hypertension before age 50.

Maternal vascular malperfusion of the placental bed associated with hypertensive disorders in the Boston Birth Cohort

IntroductionThe associations of maternal conditions, before or during pregnancy, with placental lesions have not been adequately studied in populations. MethodsIn the Boston Birth Cohort, we evaluated associations between three maternal medical conditions (hypertensive disorders [HDs], gestational/pre-gestational diabetes and obesity), and placental histological findings, using a standardized classification system proposed by the Amsterdam Placental Workshop Group. Placental pathology diagnoses and clinical data from 3074 mothers with clinical indications who delivered singleton live births at the Boston Medical Center between October 1998 and November 2013 were evaluated. Associations between each maternal condition and maternal vascular malperfusion (MVM) of the placental bed and its standardized subgroups were examined using multivariate logistic and multinomial regressions. ResultsWomen with HDs (chronic hypertension, eclampsia, preeclampsia, HELLP syndrome) had significantly increased odds of MVM lesions when compared to women with no HD (aOR 2.08 95% CI 1.74–2.50), after adjusting for demographics, substance use, diabetes and body mass index. No significant differences in frequencies or aORs were seen in women with and without diabetes, or across body mass index categories. Co-morbid condition patterns that included HDs were more likely to be associated with MVM than those without. DiscussionUsing a standardized classification system, we showed that MVM is strongly and specifically associated with maternal HDs, but not other maternal conditions. Additional studies are needed to confirm and validate our findings, and evaluate the role of maternal vascular lesions of the placental bed in relation to postnatal growth and development of the offspring and effect modifiers.

The placental component and obstetric outcome in severe preeclampsia with and without HELLP syndrome

ObjectiveWe aimed to compare obstetric outcome and placental-histopathology in pregnancies complicated by preeclampsia with severe features with and without HELLP syndrome. MethodsLabor, maternal characteristics, neonatal outcome and placental histopathology of pregnancies complicated with severe preeclampsia during 2008–2015 were reviewed. Results were compared between those without signs of HELLP syndrome (severe preeclampsia group) and those with concomitant HELLP syndrome (HELLP group). Placental lesions were classified to maternal vascular lesions consistent with malperfusion, fetal vascular lesions consistent with fetal thrombo-occlusive disease, and inflammatory lesions. Small-for-gestational-age (SGA) was defined as birth-weight ≤10th% and ≤5th%. Composite adverse neonatal outcome was defined as one or more early neonatal complications. ResultsCompared to the severe preeclampsia group (n = 223), the HELLP group (n = 64) was characterized by earlier gestational-age, 34.1 ± 2.7 vs. 35.3 ± 3.4 weeks, p = 0.010, higher rates of multiple pregnancies (p = 0.024), and thrombophilia (p = 0.028). Placentas in the HELLP group had higher rates of vascular and villous lesions consistent with maternal malperfusion (p = 0.023, p = 0.037 respectively). By multivariate logistic regression analysis models, vascular and villous lesions of maternal malperfusion were independently associated with HELLP syndrome (aOR 1.9, aOR 1.8, respectively). SGA was also more common in the HELLP group, both below the 10th percentile (p = 0.044) and the 5th percentile (p = 0.016). Composite adverse neonatal outcome did not differ between the groups. ConclusionSevere preeclampsia and HELLP syndrome have similar placental histopathologic findings. However, HELLP syndrome is associated with higher rates of placental maternal vascular supply lesions and SGA suggesting that the two clinical presentations share a common etiopathogenesis, with higher placental dysfunction in HELLP syndrome.

365: Pregnancy outcome and placental pathology in gestational and pre-gestational diabetes mellitus compared with non-diabetic controls with and without hypertensive complications

To compare pregnancy outcome and placental pathology in pregnancies complicated by diabetes mellitus (DM), GDMA1 and A2 and pre-gestational (PGDM) with matched non-diabetic controls. Pregnancy outcome and placental pathology from term pregnancies with DM complicated with hypertensive disorders (DM-H) were compared with non-diabetic hypertensive controls (control-H), matched by mode of delivery, from 2007-2012. Data were also compared between DM patients without hypertensive disorders (DM) and healthy controls (control). Neonatal outcome parameters included mean cord pH, and ICU admission rate. Composite neonatal outcome was defined as one or more of early complications: respiratory distress or need of ventilation support, hypoglycemia, phototherapy, transfusion, hypoxic-ischemic encephalopathy. Placental lesions were classified as lesions of maternal and fetal vascular supply and maternal and fetal inflammatory responses. A total of 228 patients included. DM-H patients (n=51) had higher birthweight as compared with control-H group (n=51). Composite neonatal outcome and rate of placental maternal and fetal vascular lesions did not differ between the groups. DM patients without hypertensive complications (DM, n=177)) had higher maternal age, rate of induction of labor, and birth weight compared to controls, p=0.032, p<0.001, p=0.037, respectively. Worse composite neonatal outcome was observed in the DM group compared to healthy controls, 24.3% vs. 15.2% respectively, p=0.032. Higher rate of placental maternal vascular lesions and distal villous immaturity were demonstrated in the DM vs. control group, p=0.004, p=0.014, respectively. Worse neonatal outcome and higher rate of placental vascular lesions express underlying placental pathology in diabetic women. High background rate of placental vascular lesions in hypertensive disorders, may explain the lack of difference between DM-H and controls-H.

The placental component in early‐onset and late‐onset preeclampsia in relation to fetal growth restriction

To identify pathological placental differences between early-onset and late-onset preeclampsia, in relation to fetal growth restriction (FGR). Placentas from patients with preeclampsia were analyzed for lesions of maternal vascular supply consistent with maternal underperfusion and lesions of fetal vascular supply consistent with fetal thrombo-occlusive disease. Findings were compared between patients who gave birth before 34 weeks (early-onset preeclampsia) and after 34 weeks (late-onset preeclampsia). Compared with the late-onset group (n = 93), the early-onset group (n = 37) had higher rates of FGR (62.2% vs 25.8%, P < 0.001) and lesions of maternal vascular supply (95% vs 60%, P < 0.001). Within the early-onset group, cases with FGR (n = 23) had more lesions of fetal vascular supply (47.8% vs 7%, P = 0.01), with similar high rates of lesions of maternal vascular supply (91% vs 100%) compared with those without FGR. Within the late-onset preeclampsia group, cases with FGR (n = 24) had higher rates of maternal vascular supply lesions (88% vs 51%, P = 0.003) than those without FGR, but similar rates of fetal vascular supply lesions (25% vs 16%, P = 0.32). The placental fetal vascular supply lesions in combination with maternal vascular lesions are more dominant in early-onset preeclampsia with FGR as compared with early-onset preeclampsia without FGR.

An episode of preterm labor is a risk factor for the birth of a small-for-gestational-age neonate

Patients with an episode of preterm labor that subsides in response to tocolysis and who, subsequently, deliver at term are considered to have false preterm labor. However, the episode of "preterm labor" may represent the uterine response (ie, uterine contractions) to an insult not severe enough to trigger preterm parturition, but which may put the fetus at risk for additional pregnancy complications, including growth restriction. The objective of this study was to compare the frequency of small-for-gestational-age (SGA) neonates among patients with an episode of increased uterine contractility who delivered at term and those who delivered preterm. This retrospective cohort study included 849 patients. Inclusion criteria were (1) regular uterine contractions that required hospitalization, (2) intact membranes, and (3) gestational age between 20 and 36 weeks. SGA was defined as a birth weight of <10th percentile for gestational age. Placental pathologic evidence was reviewed, and the results were used to classify patients into an inflammatory cluster, vascular cluster, or both. Contingency tables, Mann-Whitney U test, and multivariate logistic regression were used for statistical analyses. A probability value of <.05 was considered significant. The prevalence of SGA neonates in the study population was 16.1% (124/772). Patients who delivered at term had a significantly higher frequency of SGA neonates than those who delivered preterm (21.5% [64/298] vs 12.7% [60/474]; P = .001); the results of placental pathologic evidence were available in 63.7% (492/772) of the patients. Patients who delivered at term had a higher frequency of fetal or maternal vascular lesions without histologic evidence of inflammation than those who delivered preterm (29.1 % [43/148] vs 18.9% [65/344]; P = .01). Term delivery after an episode of regular preterm uterine contractions was associated with an odds ratio of 2.22 (95% CI, 1.28-3.85) to deliver an SGA neonate after the statistics were controlled for confounding variables. A subanalysis limited to patients who received tocolysis showed similar results. Patients with an episode of increased uterine contractility that subsided and who deliver at term are at risk for delivering an SGA neonate, which suggests that an episode of false preterm labor is not a benign condition. We propose that insults to the fetoplacental unit may be resolved by either irreversible preterm parturition or restriction of fetal growth.

Fetal and maternal vascular lesions

Many commonly diagnosed disorders of the placenta relate to maternal and fetal blood flow and are thus common in the placentas of infants with adverse perinatal outcomes. Severe uteroplacental vascular disease may lead to extensive placental infarction and villous changes of reduced uteroplacental blood flow, a morphologic feature commonly associated with intrauterine growth restriction and fetal demise. Lesser degrees of villous change are seen in many infants with premature delivery, term, and multiple births resulting in admission to the neonatal intensive care units. Fetal vascular lesions including chorangiosis and fetal thrombotic vasculopathy are two processes that appear to be associated with increased risk of poor outcome.

Polychlorinated biphenyl (PCB) exposure produces placental vascular and trophoblastic lesions in the mink (Mustela vison): a light and electron microscopic study.

Polychlorinated biphenyls (PCBs) cross the placenta and cause fetal death in mink. No indications of impaired implantation have been reported. To study the effects of PCB on mink placental morphology, 2 groups each of 10 animals were orally exposed to Clophen A50 at 0.65 mg (low dose) and 1.3 mg (high dose) per day for 54 days, starting before mating, with 10 control animals. Placentae from mid to late gestation were examined by light and electron microscopy. In the controls, 11% of placentae were degenerate compared to 31% (low dose) and 64% (high dose) in PCB-exposed mink. All control animals exhibited implantation sites, while one animal in the low dose and four in the high-dose group exhibited none. However, there was no difference between PCB-exposed and control animals in the number of placentation sites in implanted animals. Fetal death was markedly increased in PCB-exposed mink, with only four animals (low dose) having all viable fetuses and eight (low and high dose) having a mixture of viable and dead fetuses. Nine exposed animals displayed maternal vascular lesions in the placental labyrinthine zones of viable fetuses, comprising loss and degeneration of endothelial cells, thrombi and haemorrhages. Extracellular fluid was present between the interstitial layer of maternal vessels and the syncytiotrophoblast, and there was focal degeneration of the trophoblast and fetal vasculature. It appears, therefore, that exposure of the mink placenta to PCBs affects maternal vasculature and produces degenerative changes in the trophoblast and fetal vessels, leading to fetal growth retardation or death.

Placental lesions in maternal autoimmune diseases.

We have investigated the presence and clinical implications of maternal vascular lesions and chronic villitis of unknown etiology (CVUE) in 18 placentas of 15 mothers with several autoimmune diseases (AD), including, for the first time, idiopathic thrombocytopenic purpura, autoimmune thyroid diseases, and multiple sclerosis. The group with AD had significantly more maternal vascular lesions and CVUE than the control group. We did not find lesions that could be attributed to any of the diseases in particular. The histopathologic picture was similar in these diseases, although there appears to be a spectrum in severity. Placental vascular damage with deposits of IgM, C3, and C1q was more prominent in systemic lupus erythematosus and in a patient with systemic sclerosis. In both of these diseases but not in the other conditions, these lesions were related to poor fetal outcome. Although the precise role of each of these autoimmune diseases in pregnancy and fetal outcome remains to be established, there appears to be at least one link between them represented by the presence of severe acute atherosis and heavy granular vascular deposits of IgM, C3, and C1q associated in some with poor fetal outcome. The role of CVUE remains speculative.

Chronic villitis of unknown aetiology and decidual maternal vasculopathies in sustained chronic hypertension

Ninety-six full-term placentae were examined in the study. Of the 96 pregnancies, 72 were normotensive and 24 were complicated by hypertension. Of the 24 hypertensive pregnancies, 19 patients had chronic hypertension only, and 5 had chronic hypertension with superimposed preeclampsia. The birth weights of babies were over the 25th centile of our ponderal curve in all cases. Chronic villitis of unknown aetiology (CVUE) was found in 25% of control placentae and in 26% of placentae from chronic hypertension without preeclampsia. Eighty percent of placentae of chronic hypertension with superimposed preeclampsia presented the lesion. The incidence of CVUE was significantly higher in the latter than in the other groups. The same was observed about the proportion of inflamed villi. A higher frequency of maternal vascular lesions was observed in placentae of chronic hypertension with superimposed preeclampsia. Similar incidence and severity of the above-mentioned placental lesions have been recently described in preeclamptic pregnancies. These results suggest that these lesions (CVUE and maternal vasculopathies) are related to preeclampsia and not only to maternal hypertension.

Chronic villitis of unknown aetiology and intrauterine growth-retarded infants of normal and low ponderal index

Placentae from 211 term pregnancies were studied. The placentae were divided into three groups: group I, 57 placentae from neonates with birthweight over the 25th centile of the normal birthweight curve; group II, 49 placentae from neonates whose birthweight fell between the 10th and 25th centiles of this curve, and group III, 105 placentae from neonates whose birthweights were below the 10th centile of the curve. Each of the studied groups were divided into two subgroups, one comprising those infants with a normal Ponderal Index (PI) and the other comprising those with a low PI. A higher incidence of chronic villitis and of inflamed villi was observed as the average birthweight decreased in cases with normal PI as well as in cases with low PI, the highest incidence being found in placentae from infants with harmonic intrauterine growth retardation (normal PI). The same was observed with respect to the presence of maternal vascular lesions in all groups studied. It is suggested that an infant's birthweight and crown-heel length may be affected as a consequence of the extension and severity of the placental lesions and the timing of their appearance in gestation.

Maternal Vascular Lesions in Pre-eclampsia and Intrauterine Growth Retardation

Placental bed biopsies were performed during caesarean section in a series of 137 patients. Analysis of the morphological findings confirms that vascular physiological changes were reduced in pre-eclampsia and in normotensive intrauterine growth retardation. In pre-eclampsia, acute atherosis in the decidual segments of uteroplacental arteries was a prominent feature. Intimal thickenings of the myometrial segments of the uteromaternal arteries were also noted. Normotensive intrauterine growth retardation cases were characterized by intimal thickenings of the myometrial segments of the uteroplacental arteries. Immunofluorescent investigations have demonstrated that the deep vascular stenoses were not associated with immunoglobulin deposition while in distal arterial segments displaying acute atherosis a positive immunofluorescence for IgG and fibrin and, more irregularly, for C'3 and IgM could be noted. These findings lead us to suggest that an immunological mechanism may be involved in the pathogenesis of acute atherosis.