Single Umbilical Artery Umbilical Cord Is Associated With High-Grade Distal Fetal Vascular Malperfusion.

PURPOSE AND CONTEXT: Umbilical cord abnormalities with clinical signs of cord compromise are frequently associated with fetal vascular malperfusion (FVM). Single umbilical artery (SUA) has been reported to be associated with high-grade FVM in fetal growth restriction but not in an unselected population; our study aimed to address this issue. METHODS: Clinical and placental phenotypes of 55 consecutive placentas with SUA (Group 1) were compared with those of 655 placentas with 3-vessel umbilical cord (Group 2) from patients who were in the second half of their pregnancy. The placentas were histologically examined using hematoxylin and eosin (H&E) staining and CD 34 immunostaining. KEY RESULTS: Several umbilical cord phenotypes and high-grade distal FVM, based on H&E staining and endothelial fragmentation by CD34 were significantly more common in Group 1, whereas decidual clusters of multinucleate trophoblasts were more common in Group 2. Notably, H&E staining or CD34 immunostaining evaluated separately showed that high-grade distal FVM was more common in Group 1 than in Group 2, but the difference was not statistically significant. CONCLUSIONS: SUA predisposes to remote, advanced, and recent high-grade distal villous FVM, with a pathogenesis partly different from that of stasis-induced FVM, likely related to fetal anomalies associated with SUA.

Placental fetal vascular malperfusion in congenital diaphragmatic hernia.

The success of in-utero or intrapartum treatment for congenital diaphragmatic hernia (CDH) can be impacted by poor placental function; however, this relationship has not yet been studied. To analyze placental histomorphology in CDH, the frequencies of 24 independent clinical and 48 placental phenotypes were compared. Slides from 103 CDH placentas (group 1) and 133 clinical umbilical cord (UC) compromise/anatomical UC abnormality placentas without CDH (group 2) were subjected to hematoxylin/eosin staining and CD34 immunostaining and then examined. CD34 immunostaining was performed to identify clustered distal villi with endothelial fragmentation of recent fetal vascular malperfusion (FVM). Cesarean delivery and ex utero intrapartum treatment were more common in group 1, but group 2 showed a higher frequency of statistically significant increases in other clinical phenotypes. The frequencies of large vessels and distal villous FVMs (clustered endothelial fragmentation by CD34 immunostaining, stromal vascular karyorrhexis, avascular, or mineralized villi) did not differ between the groups, but low-grade distal villous FVMs were statistically significantly more common in group 1 than in group 2, while high-grade distal villous FVMs were significantly more common in group 2 than group 1. Large vessel and distal villous FVMs were manyfold more common in both the CDH and UC compromise groups than in the general population. However, CDH placentas were more likely to show low-grade distal villous FVMs and less likely to show high-grade distal villous FVMs in UC compromise placentas. FVM of CDH may therefore be caused by a similar pathomechanism as that of UC compromise, resulting in impaired placental fetal blood outflow.

CD34 immunostain increases the sensitivity of placental examination for distal fetal vascular malperfusion in liveborn infants.

INTRODUCTION: Placental fetal vascular malperfusion (FVM) is associated with increased perinatal morbidity and mortality. This retrospective observational analysis was performed to compare the impact of large proximal vessel (global) FVM, established/remote distal villous FVM, and recent (acute) FVM diagnosed by clustered endothelial fragmentation by CD34 immunostaining, on clinical and other placental phenotypes. METHODS: Clinical and placental phenotypes of 581 consecutive high-risk pregnancies with a live birth divided in five groups based on presence and type of FVM were analyzed. CD34 immunostaining was performed on all cases to refine the diagnosis of FVM. The statistical analysis was by ANOVA and Chi square. RESULTS: FVM was present in 88% of placentas from pregnancies dominated by congenital anomalies. 43% of those had global FVM (partial, large proximal vessel) without distal villous changes, either acute (endothelial fragmentation) or established (avascular villi). Acute distal villous FVM without avascular villi did not link with significant perinatal morbidity/mortality, likely because of its short duration. Established distal villous FVM with active endothelial fragmentation, labelled as FVM with temporal heterogeneity, is associated with preterm births, preeclampsia, abnormal Dopplers, fetal growth restriction, highest cesarean section rate, and high grade FVM, particularly the latter. DISCUSSION: Lesions of global FVM are common, featuring relatively low sensitivity for perinatal complications. Caution is indicated in assigning significance to isolated lesions such as fetal vascular ectasia, intramural fibrin deposition and stem vessel obliteration. Established and on-going FVM diagnosed by using CD34 immunostain, is much more significant and portends the most complicated perinatal outcomes.

Patterns of placental injury in various types of fetal congenital heart disease.

OBJECTIVES: Fetal blood circulation may be modified in congenital heart disease (CHD). This retrospective analysis was performed to study whether the type of CHD is associated with specific placental pathology. METHODS: Three types of CHD based on presumed proportion of placental and systemic blood distribution in fetal circulation were analyzed: Group 1: 89 cases with low placental blood content (hypoplastic left heart syndrome, transposition of great arteries, coarctation of aorta), Group 2: 71 placentas with intermediate placental and systemic blood content due to increased intracardiac blood mixing (tetralogy of Fallot, truncus arteriosus, double inlet/outlet ventricle), and Group 3: 24 placentas with high placental blood content (tricuspid or pulmonary atresia, Ebstein anomaly). Frequencies of 27 independent clinical and 47 placental phenotypes of 184 placentas in those three groups were statistically compared. RESULTS: The most advanced gestational age at delivery, and large vessel (global) fetal vascular malperfusion (FVM) were most common in Group 1, while macerated stillbirths, neonatal mortality, abnormal amniotic fluid volume (oligohydramnios or polyhydramnios), other congenital anomalies, distal villous lesions of FVM, placental edema and amnion nodosum were most common in Groups 2 and 3, although the frequencies of placental lesions were statistically not significant. CONCLUSIONS: Left heart obstructive lesions potentially associated with brain maldevelopment show increase in lesions of global FVM (in aggregate and individually fetal vascular ectasia, stem vessel obliteration and intramural fibrin deposition) as may be seen in umbilical cord compromise. CHD with increased intracardiac blood mixing or with right heart defects is associated with average preterm gestational age at delivery and placental lesions of distal villous FVM, villous edema and amnion nodosum.

Shallow Placentation: A Distinct Category of Placental Lesions.

OBJECTIVE: Shallow placental implantation (SPI) features placental maldistribution of extravillous trophoblasts and includes excessive amount of extravillous trophoblasts, chorionic microcysts in the membranes and chorionic disc, and decidual clusters of multinucleate trophoblasts. The histological lesions were previously and individually reported in association with various clinical and placental abnormalities. This retrospective statistical analysis of a large placental database from high-risk pregnancy statistically compares placentas with and without a composite group of features of SPI. STUDY DESIGN: Twenty-four independent abnormal clinical and 44 other than SPI placental phenotypes were compared between 4,930 placentas without (group 1) and 1,283 placentas with one or more histological features of SPI (composite SPI group; group 2). Placentas were received for pathology examination at a discretion of obstetricians. Placental lesion terminology was consistent with the Amsterdam criteria, with addition of other lesions described more recently. RESULTS: Cases of group 2 featured statistically and significantly (p < 0.001after Bonferroni's correction) more common than group 1 on the following measures: gestational hypertension, preeclampsia, oligohydramnios, polyhydramnios, abnormal Dopplers, induction of labor, cesarean section, perinatal mortality, fetal growth restriction, stay in neonatal intensive care unit (NICU), congenital malformation, deep meconium penetration, intravillous hemorrhage, villous infarction, membrane laminar necrosis, fetal blood erythroblastosis, decidual arteriopathy (hypertrophic and atherosis), chronic hypoxic injury (uterine and postuterine), intervillous thrombus, segmental and global fetal vascular malperfusion, various umbilical cord abnormalities, and basal plate myometrial fibers. CONCLUSION: SPI placentas were statistically and significantly associated with 48% abnormal independent clinical and 51% independent abnormal placental phenotypes such as acute and chronic hypoxic lesions, fetal vascular malperfusion, umbilical cord abnormalities, and basal plate myometrial fibers among others. Therefore, SPI should be regarded as a category of placental lesions related to maternal vascular malperfusion and the "Great Obstetrical Syndromes." KEY POINTS: · SPI reflects abnormal distribution of extravillous trophoblasts.. · SPI features abnormal clinical and placental phenotypes.. · SPI portends increased risk of complicated perinatal outcome..

Cesarean section per se is not a risk factor for non-anatomical placenta creta.

OBJECTIVE: To investigate whether mild forms of placenta creta (MPC) are more common in placentas delivered by cesarean section for non-anatomical indications than in placentas from vaginal deliveries. METHODS: This is a retrospective clinical study in which MPC was diagnosed histologically by the presence of myometrial fibers in the decidua basalis or parietalis or in direct contact with the Rohr fibrinoid or chorionic villi. After excluding 111 cases at high risk for anatomical PC, placentas from 830 consecutive cesarean deliveries (group 1) were retrospectively statistically compared with 907 placentas from vaginal deliveries (group 2). RESULTS: Statistically significant differences were found in six independent clinical and seven placental phenotypes. More frequently, pre-eclampsia, abnormal fetal heart rate tracing and umbilical artery Dopplers, hypercoiled umbilical cord, diffuse postuterine pattern of chronic hypoxic placental injury, and clusters of avascular or mineralized chorionic villi were found in group 1, while preterm delivery, induction of labor, and histological patterns related to stillbirth were observed in group 2. CONCLUSION: MPC diagnosed in placentas from cesarean sections performed for non-anatomical indications is not statistically significantly more common than in those after vaginal delivery. Therefore, MPC may feature similar diagnostic correlations and portend a similar prognosis for future pregnancies.

Umbilical cord compromise versus other clinical conditions predisposing to placental fetal vascular malperfusion.

To study the relative importance of clinical and umbilical cord (UC) risk factors for placental fetal vascular malperfusion (FVM), 52 placentas with clinical UC compromise were compared with 204 placentas with other maternal/fetal conditions predisposing to FVM, 286 placentas with both factors, and 38 placentas with no clinical conditions or UC factors predisposing to FVM. FVM, both distal villous and global, was more common with UC compromise. Cases with isolated UC compromise were associated with more unfavorable clinical outcomes and histological distal FVM. Clinical conditions without umbilical cord compromise were not associated with increased rate of FVM.

Placental CD34 immunohistochemistry in fetal vascular malperfusion in stillbirth.

AIM: To assess the use of CD34 immunostaining in diagnosing of fetal vascular malperfusion (FVM) in stillborns. METHODS: We examined 25 independent clinical (pregnancy and fetal outcomes) and 48 placental phenotypes in 100 placentas of consecutive stillborns at ≥20 weeks of gestation. Group 1 comprised 34 cases with no distal villous FVM; Group 2 comprised 36 placentas with clustered distal villous FVM (sclerotic villi, hypovascularity, stromal vascular karyorrhexis, and/or mineralization) determined using hematoxylin-eosin staining not upgraded by CD34 immunostaining, and Group 3 comprised 30 placentas with FVM diagnosed or upgraded by CD34 immunostaining (distal villous endothelial fragmentation and/or villous hypovascularity). RESULTS: Diffuse villous lesions of fetal retention with various degrees were present in approximately 50% of the cases in all groups; however, histological evaluation for FVM was still possible in most stillborns. Abnormal clinical phenotypes were significantly less frequent than abnormal placental phenotypes of FVM (8.6% vs. 24%, respectively). Chronic hypoxic placental injury patterns, fetal blood erythroblastosis, some features of shallow placental implantation, and muscular FVM lesions were most common in Group 2. Only decidual arteriopathy (hypertrophic and or hyaline necrosis/atherosis) was most frequent in Group 3. CONCLUSION: Most distal FVM lesions can be observed on hematoxylin-eosin placental slides only several days following the inciting event. CD34 immunostaining can reveal recent distal villous lesions of FVM featuring segmental villous endothelial fragmentation for de novo diagnosis or for upgrading FVM. Routine CD34 immunostaining has demonstrated FVM to be the major pattern of placental injury in stillborns.

Placental recent/on-going foetal vascular malperfusion with endothelial fragmentation is diagnostically equivalent to established distal villous lesions of foetal vascular malperfusion.

CD34 immunostaining increases the sensitivity of placental diagnosis of foetal vascular malperfusion (FVM). This comparative retrospective study was performed to find out whether recent distal FVM lesions diagnosed with CD34 are diagnostically equivalent to remote FVM lesions diagnosed with haematoxylin-eosin (H&E). Clinical and placental phenotypes of 562 placentas from ≥ 20-week, high-risk pregnancies were analysed: Group 1-158 placentas with remote distal villous FVM (by H&E only), Group 2-142 placentas showing clustered endothelial fragmentation by CD34 immunostaining, 98 of them also with H&E distal FVM lesions (on-going, temporal heterogeneity), and Group 3-262 placentas without distal villous FVM. In Group 1, gestational age was the shortest, postnatal mortality most frequent, placental weight the smallest, and intra villous haemorrhage, erythroblasts in foetal blood, hypertrophic decidual arteriopathy, and foetal vascular thrombi most common. In Group 2, placental infarction, post-uterine pattern of chronic placental injury, and excessive extra villous trophoblasts of chorionic disc were most common (p < 0.05). In this cohort of foetuses/neonates dominated by congenital malformations, distal villous FVM was the most common pattern of placental injury, and those diagnosed by CD34 and by H&E are diagnostically/prognostically equivalent. CD34 immunostaining is therefore a powerful tool in the diagnosis of distal villous FVM.

Distal villous lesions are clinically more relevant than proximal large muscular vessel lesions of placental fetal vascular malperfusion.

BACKGROUND: Fetal vascular malperfusion (FVM) can be diagnosed on placental examination based on histology of distal placental villi and large muscular placental vessels. While histology of both those placental compartments can be low grade or high grade, it is not known if these are clinically equivalent. This retrospective study aimed to compare the impact of placental distal villous and large vessel FVM lesions on clinical and placental phenotypes. METHODS: Clinical and placental phenotypes of 479 consecutive ≥20 weeks of gestation at delivery cases of placental FVM were analyzed among 3 groups: Group 1: 86 cases with distal FVM (clusters of sclerotic distal villi and/or those with stromal vascular karyorrhexis and/or mineralization, and/or endothelial fragmentation by CD34 immunostain) without large vessel lesions; Group 2: 186 cases with large vessel lesions (fetal vascular ectasia, vascular thrombi, stem vessel obliteration, intramural fibrin deposition) without distal villous lesions; and Group 3: 207 cases showing both distal villous lesions and large fetal vessel lesions. RESULTS: Statistically significant differences (Bonferroni correction) were observed in: average gestational age at delivery 31, 35, 34 weeks, fetal growth restriction 24, 9, 25%, average placental weight 318, 413, 366 g, postuterine pattern of chronic hypoxic placental injury 12, 2, 6%, luminal vascular abnormalities in stem vessels 16, 3, 11%, and high grade FVM 33, 16, 39%, among Groups 1-3, respectively. CONCLUSION: Because of longer time needed for its development, distal FVM portends poorer prognosis for the fetus than large vessel FVM.

CD34 immunostain increases sensitivity of the diagnosis of fetal vascular malperfusion in placentas from ex-utero intrapartum treatment.

OBJECTIVES: EXIT (ex-utero intrapartum treatment) procedure is a fetal survival-increasing modification of cesarean section. Previously we found an increase incidence of fetal vascular malperfusion (FVM) in placentas from EXIT procedures which indicates the underlying stasis of fetal blood flow in such cases. This retrospective analysis analyzes the impact of the recently introduced CD34 immunostain for the FVM diagnosis in placentas from EXIT procedures. METHODS: A total of 105 placentas from EXIT procedures (48 to airway, 43 to ECMO and 14 to resection) were studied. In 73 older cases, the placental histological diagnosis of segmental FVM was made on H&E stained placental sections only (segmental villous avascularity) (Group 1), while in 32 most recent cases, the CD34 component of a double E-cadherin/CD34 immunostain slides was also routinely used to detect the early FVM (endothelial fragmentation, villous hypovascularity) (Group 2). Twenty-three clinical and 47 independent placental phenotypes were compared by χ2 or ANOVA, where appropriate. RESULTS: There was no statistical significance between the groups in rates of segmental villous avascularity (29 vs. 34%), but performing CD34 immunostain resulted in adding and/or upgrading 12 more cases of segmental FVM in Group 2, thus increasing the sensitivity of placental examination for FVM by 37%. There were no other statistically significantly differences in clinical (except for congenital diaphragmatic hernias statistically significantly more common in Group 2, 34 vs. 56%, p=0.03) and placental phenotypes, proving the otherwise comparability of the groups. CONCLUSIONS: The use of CD34 immunostain increases the sensitivity of placental examination for FVM by 1/3, which may improve the neonatal management by revealing the increased likelihood of the potentially life-threatening neonatal complications.

Temporal heterogeneity of placental segmental fetal vascular malperfusion: timing but not etiopathogenesis.

Clinicopathologic correlations of segmental villous avascularity and other histological lesions of segmental fetal vascular malperfusion (SFVM) were analyzed retrospectively to determine whether lesions of various durations reflect different etiopathogeneses. The frequencies of 25 independent clinical and 43 placental phenotypes were statistically compared by ANOVA or Chi-square among 3 groups containing a total of 378 placentas with SFVM: group 1 contained 44 cases of recent SFVM (endothelial fragmentation, villous hypovascularity by CD34 immunostain, and/or stromal vascular karyorrhexis); group 2 contained 264 cases of established SFVM (clusters of avascular villi); and group 3 contained 70 cases of remote SFVM (villous mineralization). Statistically significant differences among the three study groups (p Bonferroni < 0.002) were found in four clinical variables (gestational age, frequencies of macerated stillbirth, induction of labor, and cesarean section) and in five placental variables (frequencies of fetal vascular ectasia, stem vessel luminal vascular abnormalities, diffusely increased extracellular matrix in chorionic villi, chorionic disk extravillous trophoblast microcysts, and excessive extravillous trophoblasts in the chorionic disc). In summary, the absence of statistically significant differences between the study groups regarding the most common causes of SFVM (hypertensive conditions of pregnancy, diabetes mellitus, fetal anomalies, and clinical and pathological features of umbilical cord compromise) is evidence that the three types of SFVM reflect temporal heterogeneity rather than etiopathogenesis. This evidence can be used to date the onset of fetal vascular malperfusion before delivery or stillbirth. The coexistence of different SVFM lesions of various durations indicates ongoing or repeat occurrences of FVM rather than single episodes.

Placenta Creta: A Spectrum of Lesions Associated with Shallow Placental Implantation.

BACKGROUND: On placental histology, placenta creta (PC) ranges from clinical placenta percreta through placenta increta and accreta (clinical and occult) to myometrial fibers with intervening decidua. This retrospective study aimed to investigate the clinicopathologic correlations of these lesions. METHODS: A total of 169 recent consecutive cases with PC (group 1) were compared with 1661 cases without PC examined during the same period (group 2). The frequencies of 25 independent clinical and 40 placental phenotypes were statistically compared between the groups using chi-square test or analysis of variance where appropriate. RESULTS: Group 1 placentas, as compared with group 2 placentas, were statistically significantly (p < 0.05) associated with caesarean sections (11.2% vs. 7.5%), antepartum hemorrhage (17.7% vs 11.6.%), gestational hypertension (11.2% vs 4.3%), preeclampsia (11.8% vs 2.6%), complicated third stage of labor (18.9% vs 6.4%), villous infarction (14.2% vs 8.9%), chronic hypoxic patterns of placental injury, particularly the uterine pattern (14.8%, vs 9.6%), massive perivillous fibrin deposition (9.5% vs 5.3%), chorionic disc chorionic microcysts (21.9% vs 15.9%), clusters of maternal floor multinucleate trophoblasts (27.8% vs 21.2%), excessive trophoblasts of chorionic disc (24.3% vs 17.3%), segmental fetal vascular malperfusion (27.8% vs 19.9%), and fetal vascular ectasia (26.2% vs 15.2%). CONCLUSION: Because of the association of PC with gestational hypertensive diseases, acute and chronic placental hypoxic lesions, increased extravillous trophoblasts in the chorionic disc, chorionic microcysts, and maternal floor trophoblastic giant cells, PC should be regarded as a lesion of abnormal placental implantation and abnormal trophoblast invasion rather than decidual deficiency only.

XY Gonadal Dysgenesis in a Phenotypic Female Identified by Direct-to-Consumer Genetic Testing.

We report a 16-year-old phenotypic female with 46,XY complete gonadal dysgenesis and metastatic dysgerminoma, unexpectedly discovered through direct-to-consumer (DTC) commercial genetic testing. This case underscores the importance of timely interdisciplinary care, including psychosocial intervention and consideration of gonadectomy, to optimize outcomes for individuals with differences of sex development. Her unique presentation highlights the implications of DTC genetic testing in a new diagnostic era and informs general pediatricians as well as specialists of nongenetic services about the value, capabilities, and limitations of DTC testing.

Lymphocytic Colitis With Increased Apoptosis: A Marker of Mutation in T-Cell-Mediated Immunity?

Lymphocytic colitis is a subtype of microscopic colitis that is mostly seen in adults. It presents mainly as chronic nonbloody diarrhea, with the hallmark of normal or near-normal endoscopy. In this case series, we are presenting 4 pediatric patients with lymphocytic colitis with prominent apoptosis of the colonic gland epithelium. Remarkably, all the patients have genetic mutations known to be associated with autoimmune enteropathy. Three patients have a CTLA4 mutation, and 1 patient has an STAT3 mutation. These mutations were previously reported in association with inflammatory bowel disease, but a specific connection with lymphocytic colitis has not been described. This report investigates the histopathology of such lesions in children and adolescents.

"DIY" Silica Nanoparticles: Exploring the Scope of a Simplified Synthetic Procedure and Absorbance-Based Diameter Measurements.

In this study, the classical Stöber silica synthesis protocol was used to test the limits of simplification in the preparation and size determination of nanoparticles. The scope of three-ingredient, one-pot synthesis was established in conditions of regular 96% and 99.8% ethanol as solvent, with aqueous ammonia as the only source of base and water. Particles with diameters in the 15-400 nm range can be reliably obtained with this straightforward approach, and the direct relationship between the size and the product of concentrations of water and ammonia is evidenced. Furthermore, the idea of a linear approximation for Mie scattering in particular conditions is discussed, using experimental data and theoretical calculations. A simple, fast method for particle size determination utilizing a UV-Vis spectrophotometer-an easily accessible instrument-is explained, and shows a level of error (<0.5 SD) that can be acceptable for less rigorous laboratory use of nanoparticles or serve as a quick means for testing the influence of minor alterations to known synthetic protocols. This work aims to show that nanoparticle synthesis can (and should) become a regular occurrence, even in non-specialized labs, facilitating research into their new applications and inspiring outside-the-box solutions, while discussing the drawbacks of a more relaxed synthetic regimen.

Segmental villous mineralization: A placental feature of fetal vascular malperfusion.

INTRODUCTION: This retrospective analysis was performed to find out if clusters of mineralized chorionic villi can be regarded as an independent feature of fetal vascular malperfusion (FVM). METHODS: Of all 1698 placentas reviewed by the author during the last 10 years, 39 (2.3%) showed clusters of mineralized chorionic villi (Group 1), 100 cases (5.9%) showed randomly scattered mineralized chorionic villi with without clustering (Group 2), and the remaining 1559 placentas showed no villous mineralization (comparative Group 3). In doubtful cases, histochemistry stains were performed to determine the pattern of villous mineralization. Twenty three independent clinical and 43 placental variables were statistically compared among the groups: descriptive statistics (Chi-square, Fisher test or signed rank test), and logistics regression model. RESULTS: Clinically, Group 1 featured shorter gestational age than Group 2, and in addition to shorter gestational age, more common oligohydramnios, polyhydramnios, induction of labor, macerated stillbirth and fetal growth restriction than Group 3. Of placental variables, fetal vascular ectasia, and clusters of avascular chorionic villi were more common in Group 1 than in Group 2, and in addition, segmental villous stromal vascular karyorrhexis was more common than in Group 3. By the logistics regression mode, segmental villous mineralization was independently associated with other histological features of FVM as a group and particularly with clusters of sclerotic chorionic villi. DISCUSSION: FVM is characterized by temporal heterogeneity, i.e. coexistence of lesions of various duration, and strongly and independently correlates with clusters of mineralized chorionic villi. Therefore, segmental villous mineralization should be included into the category of segmental FVM. It can be seen even in totally fibrotic placentas of prolonged stillbirth when other histological features of segmental vascular malperfusion can be obscured by global villous sclerosis.

Patterns of Placental Injury in Congenital Anomalies in Second Half of Pregnancy.

BACKGROUND: Placental pathology in fetal congenital anomalies in second half of pregnancy is largely unknown. METHODS: Twenty-six clinical and 45 independent placental phenotypes from pregnancies ≥20 weeks of gestation with congenital anomalies divided into 4 groups were retrospectively compared with analysis of variance or χ 2 with 3 degrees of freedom and with Bonferroni correction for multiple comparisons: group 1 : 112 cases with heart malformations (with or without chromosomal anomalies), group 2 : 41 cases with abnormal karyotypes and anomalies other than heart malformations, group 3 : 87 cases with intrathoracic or intraabdominal mass-forming anomalies (mostly congenital diaphragmatic hernias and adenomatoid airway malformation), and group 4 : 291 miscellaneous cases with mostly skeletal, renal, and central nervous system anomalies not fulfilling the criteria of inclusion into groups 1 to 3. RESULTS: Eight of 26 clinical (30.8%) and 16 of 45 (35.5%) placental phenotypes varied statistically significantly among the 4 groups (P < .05), of those, 7 (26.9%) and 4 (8.9%), respectively, remained statistically significant after Bonferroni correction (P Bonferroni ≤ .002). Those placental phenotypes were placental weight, chorionic disc chorionic microcysts, fetal vascular ectasia, and luminal vascular abnormalities of chorionic villi. CONCLUSIONS: Fetal anomalies in second half of pregnancy feature abnormal clinical phenotypes much more frequently than abnormal placental phenotypes. Chromosomal abnormalities with or without heart malformations tend to feature villous edema, and erythroblastosis of fetal blood, likely due to fetal heart failure. Mass-forming fetal anomalies feature placental histological lesions of shallow placental implantation, diffuse chronic hypoxic patterns of placental injury, and lesions of fetal vascular malperfusion, likely stasis-induced.

CD34 immunostain increases the sensitivity of placental diagnosis of fetal vascular malperfusion in stillbirth.

INTRODUCTION: Postmortem regressive placental changes of stillbirth may obscure the pre-existing placental histomorphology. The objective is to find out whether the use of CD34 immunostain can increase the sensitivity of placental examination in the diagnosis of fetal vascular malperfusion (FVM). METHODS: Twenty six independent clinical and 46 placental variables of 46 placentas from stillbirths were statistically compared to those of 92 placentas from livebirths. One histologically most unremarkable section per case was stained using double E-cadherin/CD34 immunostain (ECCD34). Clusters of avascular/hypovascular chorionic villi on hematoxylin and eosin (H&E) staining system and/or CD34 immunostaining, the latter also including endothelial CD34 positive debris in the villous stroma, were regarded as evidence of FVM. RESULTS: The gestational age and cesarean section rate were statistically significantly lower and the induction of labor and mild erythroblastosis of fetal blood was higher, but the frequencies of clinical and placental features of umbilical cord compromise were not statistically significant between stillbirths and livebirths, respectively. By using H&E stain, 9 (19.6%) of stillbirths and 30 (32.6%) of livebirths showed clusters of avascular villi on H&E. By CD34, the rates of FVM increased to 23 (50%) and 34 (40%), respectively. The increase was statistically significant for stillbirths only (Chi square = 9.4, p = 0.002). By CD34, new clusters of hypovascular chorionic villi or villi with endothelial fragmentation were found in 23 stillbirth cases (50%) as opposed to livebirths (29 cases, 31.5%)(Chi square = 9.4, p = 0.002). DISCUSSION: When compared with H&E stain, the CD34 increases sensitivity and/or upgrades FVM in placental examination in stillbirths but not in livebirths.