Postpartum antihypertensive treatment: Is there a correlation to placental lesions?

OBJECTIVE: We aimed to examine the association of clinical risk factors and placental lesions, in gestations complicated with preeclampsia, with the need for antihypertensive treatment in the early postpartum period. METHODS: The computerized files and placental reports of all singleton deliveries at 24.0-42.0 weeks complicated by preeclampsia were reviewed between January 2013 and October 2020. Obstetric characteristics and placental lesions were compared between patients who required antihypertensive treatment in the early postpartum period and those who did not (control group). Placentas were classified into maternal and fetal malperfusion lesions and inflammatory responses. RESULTS: As compared to controls (n = 200), the anti-hypertensive treatment group (n = 95) was characterized by increased rates of preterm birth, preeclampsia with severe features, and cesarean delivery (p < 0.001 for all). More placental hematomas (p = 0.01) and placental maternal vascular lesions (p = 0.03) were observed in the antihypertensive treatment group as compared to controls. In adjusted logistic regression analysis, gestational age (OR 0.86, 95% CI 0.79-0.93, p = 0.001) and preeclampsia with severe features (OR 8.89, 95% CI 3.18-14.93 p < 0.001) were found to be independently associated with the need for postpartum antihypertensive treatment. CONCLUSION: Placental vascular lesions are more common in preeclamptic patients who need postpartum antihypertensive treatment, yet only early onset of preeclampsia with severe features was found to be independently associated with antihypertensive treatment in the early postpartum period.

Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology.

BACKGROUND: The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known. OBJECTIVE: To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion. STUDY DESIGN: This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion. RESULTS: 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions. CONCLUSION: Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders.

The etiology of preeclampsia.

Preeclampsia is one of the "great obstetrical syndromes" in which multiple and sometimes overlapping pathologic processes activate a common pathway consisting of endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. This article reviews the potential etiologies of preeclampsia. The role of uteroplacental ischemia is well-established on the basis of a solid body of clinical and experimental evidence. A causal role for microorganisms has gained recognition through the realization that periodontal disease and maternal gut dysbiosis are linked to atherosclerosis, thus possibly to a subset of patients with preeclampsia. The recent reports indicating that SARS-CoV-2 infection might be causally linked to preeclampsia are reviewed along with the potential mechanisms involved. Particular etiologic factors, such as the breakdown of maternal-fetal immune tolerance (thought to account for the excess of preeclampsia in primipaternity and egg donation), may operate, in part, through uteroplacental ischemia, whereas other factors such as placental aging may operate largely through syncytiotrophoblast stress. This article also examines the association between gestational diabetes mellitus and maternal obesity with preeclampsia. The role of autoimmunity, fetal diseases, and endocrine disorders is discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention.

Are there gender-specific differences in pregnancy outcome and placental abnormalities of pregnancies complicated with small for gestational age?

INTRODUCTION: Adaptations to pathological intrauterine environment might differ in relation to fetal gender. We aimed to study sex-specific differences in placental pathology of pregnancies complicated by small for gestational age (SGA). METHODS: The medical records and placental histology reports of all neonates with a birth-weight ≤ 10th percentile, born between 24 and 42 weeks of gestation, during 2010-2018, were reviewed. Composite neonatal outcome was defined as one or more of early following complications: neonatal sepsis, blood transfusion, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis, or death. Results were compared between the male and female groups of neonates. Placental lesions were classified into maternal and fetal vascular malperfusion (MVM and FVM) lesions, maternal and fetal inflammatory responses (MIR and FIR), and villitis of unknown etiology (VUE). RESULTS: The male SGA group (n = 380) and the female SGA group (n = 363) did not differ in regard to maternal age, BMI, smoking, associated pregnancy complications, gestational age, and mode of delivery. Neonates in the SGA male group had increased birth-weight and increased respiratory morbidity as compared to the female SGA group (p = 0.007, p = 0.005, respectively). There was no between-group differences in the rate of placental lesions. By multivariate logistic regression analysis, male gender (aOR 1.55, 95% CI 1.05-2.30, p = 0.025), FIR (aOR 4.83, 95% CI 1.07-13.66, p = 0.003), and VUE (aOR 1.89, 95% CI 1.03-3.47, p = 0.04), were found to be independently associated with adverse composite neonatal outcome. DISCUSSION: Male gender as well as placental FIR and VUE are independently associated with adverse neonatal outcome in SGA neonates.

Pathologic placental lesions in early and late fetal growth restriction.

INTRODUCTION: The purpose of the study was to evaluate the differences in individual histopathologic placental lesions in pregnancies complicated by early-onset (<32 weeks at diagnosis) and late-onset (≥32 weeks at diagnosis) fetal growth restriction (FGR). MATERIAL AND METHODS: A cohort study of 440 singleton pregnancies complicated by FGR, diagnosed according to standard ultrasonographic criteria, followed up and delivered at the same institution between 2010 and 2016. Placental lesions were classified according to the Amsterdam Placental Workshop Consensus Criteria. Pathologic examination of placentas from 113 healthy singleton term pregnancies served as controls. Binary and multinomial logistic regression models were used to evaluate the independent association of placental lesions with the type of FGR. RESULTS: In our cohort the prevalences of early and late FGR were 37.3% (164/440) and 62.7% (276/440), respectively. The overall rates of preeclampsia (69/164 vs 59/276, P < 0.01) and absent/reversed umbilical artery pulsatility indices (61/164 vs 14/276, P < 0.001) were higher among early FGR than late FGR. Placental characteristics from early and late FGR pregnancies differed mainly in regard to maternal vascular malperfusion scores rather than fetal scores, with preeclampsia found to be a cofactor modulating the rates and severity of associated lesions. In the binary logistic analysis, recent infarcts (OR 2.44, 95% CI 1.2-5), distal villous hypoplasia (OR 1.8, 95% CI 1.0-3.2), atherosis (OR 2.71, 95% CI 1.35-5.47), persistent endovascular trophoblasts (OR 1.67, 95% CI 1.03-2.7), and a reduced fetal/placental weight score (OR 0.27, 95% CI 0.2-0.38) were independently associated with an increased likelihood of early FGR compared with late FGR. The sensitivity, specificity, and area under the curve of the model were 60% (95% CI 51.2-66.2), 89.1% (95% CI 84.9-92.3), and 0.81 (95% CI 0.77-0.85), respectively, suggesting a fair to good predictive value. CONCLUSIONS: Individual placental lesions suggestive of increased rates of ischemia, defective remodeling of spiral arteries, peripheral hypoxia interfering with villus development, and reduced placental efficiency were significantly more common in early FGR than late FGR.

Placental pathology lesions: International Society for Ultrasound In Obstetrics And Gynecology vs. Society for Maternal-Fetal Medicine Fetal growth restriction definitions.

BACKGROUND: Research on the definition of fetal growth restriction has focused on predicting adverse perinatal outcomes. A significant limitation of this approach is that the individual outcomes of interest could be related to the condition and the treatment. Evaluation of outcomes that reflect the pathophysiology of fetal growth restriction may overcome this limitation. OBJECTIVE: To compare the diagnostic performance of the fetal growth restriction definitions established by the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine to predict placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome. STUDY DESIGN: In this retrospective cohort study of singleton pregnancies, the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine guidelines were used to identify pregnancies with fetal growth restriction and a corresponding control group. The primary outcome was the prediction of placental histopathological findings associated with placental insufficiency, defined as lesions associated with maternal vascular malperfusion. A composite adverse neonatal outcome (i.e., umbilical artery pH≤7.1, Apgar score at 5 minutes ≤4, neonatal intensive care unit admission, hypoglycemia, respiratory distress syndrome requiring mechanical ventilation, intrapartum fetal distress requiring expedited delivery, and perinatal death) was investigated as a secondary outcome. Sensitivity, specificity, positive and negative predictive values, and the areas under the receiver-operating-characteristics curves were determined for each fetal growth restriction definition. Logistic regression models were used to assess the association between each definition and the studied outcomes. A subgroup analysis of the diagnostic performance of both definitions stratifying the population in early and late fetal growth restriction was also performed. RESULTS: Both societies' definitions showed a similar diagnostic performance as well as a significant association with the primary (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 3.01 [95% confidence interval 2.42, 3.75]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.85 [95% confidence interval 2.31, 3.51]) and secondary outcomes (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 1.95 [95% confidence interval 1.56, 2.43]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.12 [95% confidence interval 1.70, 2.65]). Furthermore, both fetal growth restriction definitions had a limited discriminatory capacity for placental histopathological findings of maternal vascular malperfusion and the composite adverse neonatal outcome (area under the receiver-operating-characteristics curve International Society for Ultrasound in Obstetrics and Gynecology 0.63 [95% confidence interval 0.61, 0.65], 0.59 [95% confidence interval 0.56, 0.61]; area under the receiver-operating-characteristics Society for Maternal-Fetal Medicine 0.63 [95% confidence interval 0.61, 0.66], 0.60 [95% confidence interval 0.57, 0.62]). CONCLUSIONS: The International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine fetal growth restriction definitions have limited discriminatory capacity for placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome.

[Placental pathology of uteroplacental vascular deficiency]. / Anatomie pathologique de l'insuffisance vasculaire utéroplacentaire.

The indications of the pathological examination of the placenta are mainly represented by uteroplacental vascular deficiency. The clinical context is often evocative, but it can sometimes be solely an intra-uterine growth retardation or an unexplained in utero fetal death. So, the pathological lesions of this uteroplacental vascular deficiency must be well-known to be correctly interpreted, for none of these lesions is truly specific. The pathological diagnosis is based on a group of macroscopic and microscopic arguments. Various physiopathological mechanisms, often imperfectly known, can be at the origin of an uteroplacental vascular insufficiency, but in the current position, the pathological examination does not allow etiopathogenic orientation. The development of the trophoblastic biopsies gives us access to a new material which, in parallel with the cytogenetic analysis, often allows us, in front of an unexplained intra-uterine growth retardation, to direct the diagnosis towards uteroplacental vascular insufficiency. The histological analysis of the chorionic villous sampling taken precociously during pathological pregnancies is thus a major diagnostic contribution. But especially, this analysis gives access to new information which, in the near future, will enable us to better define the pathological evolution of the lesions of hypoxic chorionic villous and to contribute to a better knowledge of this pathology which, under many aspects, still conceals many mysteries.

Placental lesions associated with stillbirth by gestational age, according to feature importance: Results from the stillbirth collaborative research network.

INTRODUCTION: Previous studies have identified lesions commonly found in placentas associated with stillbirth but have not distinguished across a range of gestational ages (GAs). The objective of this study was to identify lesions associated with stillbirths at different GAs by adapting methods from the chemical machine learning field to assign lesion importance based on correlation with GA. METHODS: Placentas from the Stillbirth Collaborative Research Network were examined according to standard protocols. GAs at stillbirth were categorized as: <28 weeks (extreme preterm stillbirth [PTSB]), 28-33'6 weeks (early PTSB), 34-36'6 weeks (late PTSB), ≥37 weeks (term stillbirth). We identified and ranked the most discriminating placental features, as well as those that were similar across GA ranges, using Kernel Principal Covariates Regression (KPCovR). RESULTS: These analyses included 210 (47.2%) extreme PTSB, 85 (19.1%) early PTSB, 62 (13.9%) late PTSB, and 88 (19.8%) term stillbirths. When we compute the KPCovR, the first principal covariate indicates that there are four lesions (acute funisitis & nucleated fetal red blood cells found in extreme PTSB; multifocal reactive amniocytes & multifocal meconium found in term stillbirth) that distinguish GA ranges among all stillbirths. DISCUSSION: There are distinct placental lesions present across GA ranges in stillbirths; these lesions are identifiable using sophisticated feature selection. Further investigation may identify histologic changes across gestations that relate to fetal mortality.

Laminar Necrosis and Hypoxic Damage of the Placenta: A Case-Control Study.

The aim of this study is to verify the role of laminar necrosis (LN) in the diagnosis of hypoxic damage of the placenta. This is a retrospective case-control study in which 50 cases with laminar necrosis were compared with 100 gestational age-matched controls without laminar necrosis in a 1:2 ratio. The parameters analyzed were: the presence of other placental lesions, obstetric characteristics and neonatal outcome. For each of the 50 cases, the area affected by the lesion was detected, and the lesions were classified into three groups based on the morphology and time of onset of the lesion in order to understand whether these characteristics of the lesion had a clinical-pathology. The results showed that including the search for LN among placental lesions generally examined is useful to guide the pathologist in the diagnosis of placental dysfunction of hypoxic origin.

Severe placental lesions due to maternal SARS-CoV-2 infection associated to intrauterine fetal death.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause severe placental lesions leading rapidly to intrauterine fetal death (IUFD). From August 2020 to September 2021, in the pathology department of Toulouse Oncopole, we analyzed 50 placentas from COVID-19-positive unvaccinated mothers. The purpose of our study is to describe the clinicopathological characteristics of these placental damages and to understand the pathophysiology. Ten of them (20%) showed placental lesions with positive immunohistochemistry for SARS-CoV-2 in villous trophoblasts. In five cases (10%), we observed massive placental damage associating trophoblastic necrosis, fibrinous deposits, intervillositis, as well as extensive hemorrhagic changes due to SARS-CoV-2 infection probably responsible of IUFD by functional placental insufficiency. In five other cases, we found similar placental lesions but with a focal distribution that did not lead to IUFD but live birth. These lesions are independent of maternal clinical severity of COVID-19 infection because they occur despite mild maternal symptoms and are therefore difficult to predict. In our cases, they occurred 1-3 weeks after positive SARS-CoV-2 maternal real-time polymerase chain reaction testing and were observed in the 2nd and 3rd trimesters of pregnancies. When these lesions are focal, they do not lead to IUFD and can be involved in intrauterine growth restriction. Our findings, together with recent observations, suggest that future pregnancy guidance should include stricter pandemic precautions such as screening for a wider array of COVID-19 symptoms, enhanced ultrasound monitoring, as well as newborn medical surveillance.

Association between maternal/newborn genetic variants, placental pathology and spontaneous preterm birth risk: a Romanian population-based study.

Objective: The objective of this study was to determine the association between maternal/newborn single-nucleotide polymorphisms (SNPs) in three candidate genes, placental pathology and the risk of spontaneous preterm birth (SPTB) in a Romanian population.Methods: We performed a prospective case-control study in a tertiary maternity in Romania, including 79 mother-newborn pairs with SPTB and 81 mother-newborn pairs with term delivery. Using real-time Polymerase Chain Reaction (PCR), three SNPs rs8192282 A > G, rs2277698 C > T and rs34003 A > C located on interleukin 6 receptor (IL6R), tissue inhibitor of matrix metalloproteinase-2 (TIMP2) and fibroblast growth factor 1 (FGF1) genes were assessed. The minor allele and genotype frequencies were compared between groups. Multilocus genetic association analyses were performed. From pathology reports, the morphological and histopathological examination of the placentas were extracted.Results: The rs34003 C/C genotype frequency in newborns FGF1 gene was significantly higher in the spontaneous preterm birth (SPTB) group compared to the control group (p = .045). In single-locus analyses, C/C genotype was associated with an increased risk of spontaneous preterm birth (OR = 2.59, 95%CI: 1.02-6.58). Additionally, this homozygote genotype was correlated with the presence of placental pathology, especially with the inflammatory and vascular lesions (p < .01). The prediction model based on rs34003 C/C genotype - placental pathology joint influence had a statistically significant regression coefficient (p < .01, OR = 7.76, 95%CI: 4.03-14.93). Single nucleotide polymorphisms related to IL6R gene in maternal samples and FGF1 gene in newborns were associated with spontaneous preterm delivery in multilocus genetic association analyses (p = .028, OR of 2.375).Conclusions: Our results indicate that rs34003 C/C genotype in newborns FGF1gene is correlated with the occurrence of placental pathological lesions and with an increased SPTB risk. The association of two SNPs in maternal and fetal genes doubled the risk of spontaneous preterm birth in our population.

Coccidioidomycosis in pregnancy: Case report and literature review of associated placental lesions.

BACKGROUND: Coccidioidomycosis is an endemic fungal infection found most commonly in the Southwestern United States, Northwestern Mexico, and parts of Central and South America. Although infection is relatively uncommon during pregnancy, it is imperative to have an index of suspicion in order to diagnose and begin timely treatment to prevent dissemination and dire consequences. CASE REPORT: A 33-year-old Hispanic female was evaluated after she was involved in an automobile accident. Radiographic evaluation showed a 3.2 × 3.2 cm cavitary thick-walled lesion. A biopsy was negative for malignancy. Evaluation was positive for coccidioidomycosis by complement fixation reaction. Four months later, the patient presented 7 weeks into a pregnancy with massive hemoptysis. Bronchoscopy revealed bleeding from the right upper lobe and emergency embolization was performed. The patient had a spontaneous abortion 9 days after admission. The right upper and middle lobes of the lung were resected due to continuous bleeding. A subsequent pregnancy was un-eventful. Coccidioidomycosis titers remained negative throughout the second pregnancy. DISCUSSION: This case demonstrates the potential for severe pulmonary coccidioidomycosis and vascular strain of pregnancy-associated vascular expansion in the first trimester of pregnancy and the possibility of a favorable pregnancy outcome in subsequent pregnancies after appropriate treatment. The route of feto-maternal transmission and placental lesions in coccidioidomycosis are discussed.

Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction.

INTRODUCTION: Discriminating between placentally-mediated fetal growth restriction and constitutionally-small fetuses is a challenge in obstetric practice. Placental growth factor (PlGF), measurable in the maternal circulation, may have this discriminatory capacity. METHODS: Plasma PlGF was measured in women presenting with suspected fetal growth restriction (FGR; ultrasound fetal abdominal circumference <10th percentile for gestational age) at sites in Canada, New Zealand and the United Kingdom. When available, placenta tissue underwent histopathological examination for lesions indicating placental dysfunction, blinded to PlGF and clinical outcome. Lesions were evaluated according to pre-specified severity criteria and an overall severity grade was assigned (0-3, absent to severe). Low PlGF (concentration <5th percentile for gestational age) to identify placental FGR (severity grade≥2) was assessed and compared with routine parameters for fetal assessment. For all cases, the relationship between PlGF and the sampling-to-delivery interval was determined. RESULTS: Low PlGF identified placental FGR with an area under the receiver-operator characteristic curve of 0.96 [95% CI 0.93-0.98], 98.2% [95% CI 90.5-99.9] sensitivity and 75.1% [95% CI 67.6-81.7] specificity. Negative and positive predictive values were 99.2% [95% CI 95.4-99.9] and 58.5% [95% CI 47.9-68.6], respectively. Low PlGF outperformed gestational age, abdominal circumference and umbilical artery resistance index in predicting placental FGR. Very low PlGF (<12 pg/mL) was associated with shorter sampling-to-delivery intervals than normal PlGF (13 vs. 29.5 days, P < 0.0001). DISCUSSION: Low PlGF identifies small fetuses with significant underlying placental pathology and is a promising tool for antenatal discrimination of FGR from fetuses who are constitutionally-small.

Placental lesions of vascular insufficiency are associated with anti-angiogenic state in women with preeclampsia.

OBJECTIVE: To evaluate if placental histopathological changes of vascular insufficiency correlate with circulating angiogenic factors in patients with preeclampsia. MATERIALS AND METHODS: Subjects were selected from a previous prospective cohort study of preeclampsia based on the availability of plasma anti-angiogenic factor (sFlt1) and pro-angiogenic factor (PlGF) measurements and placental histology specimens. Preeclamptic patients were divided into two groups based on plasma levels of these factors described as a ratio: anti-angiogenic preeclampsia with sFlt1/PlGF ratio ≥85 and normal angiogenic preeclampsia with sFlt1/PlGF < 85. The placental lesions of vascular insufficiency that were studied specifically included atherosis, infarcts, syncytial knots, acute and chronic abruption, hematoma, and fetal thrombosis. The data are shown as median (quartile 1 and quartile 3) or n (%) when appropriate. RESULTS: The anti-angiogenic preeclampsia group (N = 48) presented at an earlier gestational age (weeks) than the normal angiogenic group (N = 28); {32 (28, 34) versus 35 (32, 36), p = 0.002}, had higher systolic blood pressure (mmHg) {154 (147, 168) versus 147 (132, 158), p = 0.02}, delivered early (weeks) {(32 (29, 34) versus 36 (34, 37), p < 0.001} and had lower birth weight (grams) {(1550 (1055, 2060) versus 2655 (2285, 3343), p < 0.001}. Several pathologic lesions were found significantly more often in the anti-angiogenic preeclampsia group; atherosis {27.7% versus 3.6%, p < 0.05}, infarcts {58.3% versus 3.6%, p = 0.002}, and syncytial knots {81.3% versus 39.3%, p < 0.001}. CONCLUSION: Preeclamptic patients with imbalance in circulating angiogenic factors have disproportionally higher rates of placental vascular lesions historically associated with severe disease.

Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion.

OBJECTIVE: This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP). METHODS: In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters. RESULTS: A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p = 0.008). DISCUSSION: Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates. CONCLUSIONS: Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.

Placental lesions associated with abortion and stillbirth in goats naturally infected by Neospora caninum / Lesões placentárias associadas a abortos e natimortos em cabras naturalmente infectadas pelo Neospora caninum

Neospora caninum has been described as a parasite that sporadically causes reproductive problems in goats. Several aspects of the pathogenesis of neosporosis in naturally infected goats remain to be established. The aims of the present study were to characterize the placental lesions in goats naturally infected by N. caninum and to evaluate several diagnostic techniques for effective detection of this protozoan in the goat placenta. Some placentas in this study originated from abortion and stillbirth in which there were severe lesions. The lesions were characterized mainly by necrosis involving the mesenchyme of the chorionic villi and trophoblast cells often alongside mononuclear inflammation and in some cases with neutrophilic infiltration. N. caninum DNA was detected in these placentas, but parasite structures were not visualized through immunohistochemistry (IHC). However, five of 11 placentas from N. caninum-infected goats that gave birth to healthy kids had histological lesions characterized by mononuclear inflammation. Of these 11 placentas, N. caninum DNA was detected in seven, and N. caninum tachyzoites were detected in only one of these seven placentas using IHC. The present study demonstrates that severe lesions in the placenta are associated with abortion and stillbirth in caprine neosporosis and the placental alterations are likely involved in abortion pathogenesis. Moreover, the results highlight the importance of using more than one diagnostic technique for the detection of the protozoan in placentas because N. caninum cannot be reliably detected by histological and immunohistochemical tests.(AU)

Neospora caninum é descrito como um parasito que causa problemas reprodutivos esporádicos em cabras. Muitos aspectos da patogênese da neosporose em cabras naturalmente infectadas ainda precisam ser estabelecidos. Os objetivos deste trabalho foram caracterizar as lesões placentárias em cabras naturalmente infectadas por N. caninum e avaliar as técnicas diagnósticas para a detecção efetiva do protozoário na placenta. Algumas placentas deste estudo são originárias de abortos e natimortos, nas quais havia lesões graves. As lesões foram classificadas principalmente por necrose envolvendo o mesênquima das vilosidades coriônicas e células trofoblásticas, geralmente associadas a infiltrado inflamatório mononuclear e em alguns casos infiltrado neutrofílico. O DNA do N. caninum foi detectado nestas placentas, porém estruturas parasitárias não foram visualizadas na imuno-histoquímica (IHQ). Entretanto, cinco das onze placentas de cabras infectadas, que deram à luz a conceptos saudáveis, apresentaram lesões histológicas caracterizadas por infiltrado inflamatório mononuclear. Destas 11 placentas, foi detectado DNA de N. caninum em sete e taquizoítos foram encontrados em apenas uma por meio de imuno-histoquímica. O presente estudo demonstra que abortos e natimortos na espécie caprina, causados pelo N. caninum estão associados a lesões acentuadas nas placentas, sendo que as mesmas estão envolvidas na patogênese do aborto. Os resultados também ressaltam a importância do uso de mais de uma técnica diagnóstica para a detecção do protozoário em placentas, pois o N. caninum não pode ser confiavelmente detectado somente pelos exames de histopatologia e imuno-histoquímica.(AU)

Placental findings in late-onset SGA births without Doppler signs of placental insufficiency.

OBJECTIVES: To describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. METHODS: A series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation. RESULTS: A total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161). DISCUSSION: In most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease. CONCLUSIONS: A significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency.