Clinical Significance of the Large Fetal Vessel Lesions in Placental Fetal Vascular Malperfusion.

Fetal vascular malperfusion (FVM) is an important pattern of placental injury. Although the significance of distal villous FVM (clusters of sclerotic and/or mineralized chorionic villi) is well documented, the clinical significance of proximal (large vessel) lesions of FVM is less clear, which is the aim of this retrospective analysis. To evaluate the clinical significance and placental associations of single and coexisting categories of lesions of large vessel FVM, 24 clinical and 44 placental phenotypes of 804 consecutive placentas with at least 1 lesion of proximal vessel FVM from the second half of pregnancy, divided according to the type or category of the individual FVM lesion (fetal vascular ectasia, fetal vascular thrombi, intramural fibrin deposition, and stem vessel obliteration): 689, 341, 286, and 267 placentas, respectively (first analysis) and single or coexisting large fetal vessel lesions (1, 2, 3, and 4 coexisting categories of lesions: 276, 321, 162, and 45 placentas, respectively) were statistically compared (analysis of variance, χ2, univariate analysis). Because of multiple comparisons, Bonferroni-corrected P < .001 was used as a threshold of statistical significance. In this population of high-risk pregnancies dominated by fetal congenital anomalies, single individual or 1 to 2 coexisting categories of lesions of the large vessel FVM, including fetal vascular thrombi, did not consistently correlate with clinical or placental variables and were not prognostically useful, but the coexistence of 3 or 4 lesions was associated with the most advanced gestational age, fetal congenital anomalies, distal villous FVM, particularly high-grade, chorangioma or chorangiomatosis, hypercoiled umbilical cord, perivascular stem edema, and marginate or vallate placenta. Therefore, the finding of multiple lesions of the large vessel FVM not only merits a diligent search for the distal villous lesions including the CD34 immunostaining, but also justifies putting the large vessel (global) FVM on the final placental diagnosis line, which in the case of up to only 2 lesions may not be justified.

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.

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..

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.

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.

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.

A first case of hepatocellular carcinoma in the baboon (Papio spp.) placenta.

We present a case of hepatocellular carcinoma (HCC) in the placenta of healthy baboon (Papio spp.). Grossly, the fetal, maternal, and placental tissues were unremarkable. Histologically, the placenta contained an unencapsulated, poorly demarcated, infiltrative, solidly cellular neoplasm composed of cells that resembled hepatocytes. The neoplastic cells were diffusely positive for vimentin and focally positive for Ae1/Ae3, Arginase -1, glutamine synthetase, and CD10, and negative for ER, vascular markers (CD31 and D240), S100, glypican, C-reactive protein, FABP, desmin, and beta-catenin; INI1 positivity was similar to non-neoplastic tissues. The case likely represents a unique subtype of HCC.

Histological Features of Shallow Placental Implantation Unify Early-Onset and Late-Onset Preeclampsia.

Preeclampsia is distinguishable from other hypertensive conditions of pregnancy by its high rates of decidual arteriopathy, the uterine type of chronic hypoxic placental injury, the occurrence of villous infarctions, and clusters of multinucleate trophoblasts in the maternal floor. To retrospectively study the clinical and placental phenotypes of 230 women with early-onset preeclampsia, 261 women with late-onset preeclampsia, and 5059 women without hypertension in pregnancy (comparative group), 24 clinical and 46 placental phenotypes were statistically compared (analysis of variance, χ2 with Bonferroni correction). The frequency of decidual arteriopathy (both hypertrophic and atherosis), patterns of chronic hypoxic placental injury, villous infarction, membrane laminar necrosis, membrane microscopic chorionic pseudocysts, clusters of maternal floor multinucleated trophoblasts, excessive number of extravillous trophoblasts, and intervillous thrombi was strikingly higher in both late-onset preeclampsia and early-onset preeclampsia than in the comparative group without hypertension in pregnancy. All 3 patterns of chronic hypoxic placental injury were 2- to 3-fold more common in preeclampsia. Although the preuterine pattern was as common in early-onset preeclampsia as it was in late-onset preeclampsia, the postuterine pattern was 2-fold more common in early-onset preeclampsia, and chronic villitis of unknown etiology was more common in late-onset preeclampsia than in the other 2 groups. Features of shallow placental implantation occurred at the same frequency in early-onset preeclampsia as in late-onset preeclampsia, which reflects an underlying common pathological mechanism in both subgroups of preeclampsia, while hypoxic lesions and patterns of placental injury were more common in early-onset preeclampsia than in late-onset preeclampsia, which correlates with more severe clinical outcomes of the former.

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.

Placental examination in nonmacerated stillbirth versus neonatal mortality.

AIM: To retrospectively statistically compare clinical and placental phenotypes of nonmacerated fetuses and live-born perinatal deaths in 3rd trimester pregnancies. METHODS: Twenty-five clinical and 47 placental phenotypes were statistically compared among 93 cases of nonmacerated (intrapartum, or recent antepartum death) 3rd trimester fetal deaths (Group 1), 118 3rd trimester neonatal deaths (Group 2) and 4285 cases without perinatal mortality (Group 3). RESULTS: Sixteen clinical and placental phenotypes were statistically significantly different between Group 3 and the two groups of perinatal deaths, which included eight placental phenotypes of fetal vascular malperfusion and eight other placental phenotypes of various etiology (amnion nodosum, 2-vessel umbilical cord, villous edema, increased extracellular matrix of chorionic villi, erythroblasts in fetal blood and trophoblastic lesions of shallow placentation). Statistically significant differences between Groups 1 and 2 were scant (oligohydramnios, fetal malformations, cesarean sections, hypercoiled umbilical cord and amnion nodosum being more common in the latter, and retroplacental hematoma more common in the former). CONCLUSION: Placental examination in neonatal mortality shows thrombotic pathology related to umbilical cord compromise and features of shallow placental implantation that are similar to those in nonmacerated stillbirth; however, the features of placental abruption were more common in recent antepartum death, as were the features related to neonatal congenital malformations in neonatal deaths.

Decidual arteriolopathy with or without associated hypertension modifies the underlying histomorphology in placentas from diabetic mothers.

AIM: The aim of this study was to retrospectively document the impact of hypertensive conditions in pregnancy and decidual arteriolopathy on the patterns of placental injury in maternal diabetes mellitus (MDM). METHODS: Among all 5248 > 20 weeks' placentas, the frequencies of 19 selected clinical and 24 placental phenotypes were compared between 287 MDM placentas and 4961 remaining placentas (control group [CG]) before and after further exclusion of 85 and 611 patients with hypertensive conditions (gestational hypertension, pre-eclampsia, chronic hypertension). RESULTS: Cesarean section rate, heavy placentas, decidual arteriolopathy, microscopic chorionic pseudocysts, and chorangiosis were more common in MDM than in the CG both before and after exclusion of hypertensive conditions. The frequencies of preuterine patterns of chronic hypoxic placental injury and plasma cell deciduitis became statistically significant only after exclusion of hypertensive conditions. CONCLUSION: Hypertensive conditions of pregnancy may obscure the underlying preuterine placental hypoxic pattern in MDM placentas. Even in normotensive patients, decidual arteriolopathy, and shallow placental implantation significantly impact placental histomorphology in MDM.

An Unusual Presentation of Myositis Ossificans in a Pediatric Patient.

BACKGROUND: Myositis ossificans (MO) is a rare, non-neoplastic lesion characterized by heterotopic ossification of soft tissue. The condition is predominantly seen in young adults and adolescents and is most commonly secondary to trauma. Although the exact etiology remains unclear, patients typically present with pain and restricted range of motion following trauma or overuse. MO rarely presents in the popliteal fossa of adult patients and has not been previously reported in that of a pediatric patient. METHODS: We present a 12-year-old patient with no history of direct trauma with MO in the right popliteal fossa, a highly unusual location. Initial x-rays failed to show the lesion; however, later radiographs showed an ossified mass. At peak dimensions, the ossification measured 3.8 cm anteroposterior×2.5 cm transverse×3.2 cm craniocaudal. After 14 months of observation and conservative therapy, the mass was excised. RESULTS: The patient was ultimately able to return to full activity. Radiographs taken 14 months after the excision showed no signs of recurrence of the lesion. CONCLUSIONS: To our knowledge, this is the first reported case of MO excised from the popliteal fossa of a pediatric patient and followed for >1 year. LEVEL OF EVIDENCE: Level IV-case report.

Placental infectious villitis versus villitis of unknown etiology.

To assess the incidence, diagnosis, pathogenesis, and clinical and placental associations of congenital cytomegalovirus infection, 34 cases thereof diagnosed by placental/fetal or neonatal workup (group 1), and 494 placentas with villitis of unknown etiology (group 2) were extracted from a 6083-case placental database. 28 clinical and 47 placental phenotypes were compared between the two groups by Yates 2 or ANOVA using the Bonferroni correction. 26 group 1 cases did and 8 did not feature placental villitis, but all cases were positive as shown by immunohistochemistry and/or in situ hybridization. Only 5 differences were statistically significant (p Bonferroni < 0.0056): gestational age 29.8 ±6.5 vs. 35.5 ±4.9 weeks, perinatal mortality 67.6 vs. 16.2%, nonmacerated stillbirth 20.6 vs. 3.0%, macerated stillbirth 38.2 vs. 9.3%, and diffuse villous fibrosis 44.1 vs. 12.5%, between group 1 and group 2, respectively. The absence of significant differences in placental phenotypes between group 1 and group 2 other than the histological pattern of villitis indicates that not the cytomegalovirus villitis but the direct viral cytopathogenic effect on fetal organs makes the difference in the dire clinical outcome in the former. As about a third of cytomegalovirus infections show no villitis, the combination of the clinical picture and placental patterns creates the best chance to detect congenital cytomegalovirus infection.

Pleuropulmonary Blastoma in a Neonate Diagnosed Prenatally as Congenital Pulmonary Airway Malformation.

Pleuropulmonary blastoma is an extremely rare lung neoplasm exclusive to children under 5 years of age. It presents a diagnostic challenge both prenatally and in early childhood due to its similarity to benign lung cysts, which are managed differently. We present the first case, to our knowledge, of a neonate with pleuropulmonary blastoma and myelomeningocele, though prenatally diagnosed as a congenital pulmonary airway malformation. We detail the prenatal imaging that facilitated counseling and delivery management in addition to the correlating postnatal imaging.

Placental hypoxic overlap lesions: a clinicoplacental correlation.

AIM: This retrospective analysis is aimed to study clinical and placental associations of placental acute, chronic, and acute-on-chronic (overlap) hypoxic lesions. MATERIAL AND METHODS: Frequencies of 32 clinical (maternal and fetal) and 47 placental (gross and microscopic) phenotypes were compared by the Yates χ(2) with the Holm-Bonferroni correction among consecutive placentas from 2831 ≥ 16-week gestations: 778 placentas with chronic hypoxic lesion(s) (diffuse patterns of hypoxic placental injury, chorangiosis, excessive extravillous trophoblasts, microscopic chorionic pseudocysts, clusters of decidual multinucleate trophoblasts), 481 placentas with acute hypoxic lesion(s) (infarction, intravillous hemorrhage, deep meconium penetration, membrane laminar necrosis), 585 placentas with hypoxic overlap lesion(s) (coexisting at least one lesion from each of the above groups), and 987 placentas without placental hypoxic lesions, adjusted for gestational age. RESULTS: The control group was dominated by premature rupture of membranes, inflammatory pattern of placental injury, and poor prenatal care. The fetal and placental hypoxic patterns were associated not only with increased frequency of clinical hypoxia-associated conditions, but also abnormal umbilical cord coiling, intervillous thrombi, retroplacental hematomas, and placental features of fetal thrombotic vasculopathy, particularly in association with hypoxic overlap lesions. CONCLUSION: Placental hypoxic overlap lesions are associated with clinical complications of pregnancy and predispose to thrombotic lesions, some most likely stasis-induced.

Comparison of placental pathology in preterm, late-preterm, near-term, and term births.

OBJECTIVE: The purpose of this study was to determine whether placental pathologic condition supports the recent suggestion of subcategorizing preterm and term births into smaller gestational age subgroups with different perinatal mortality and morbidity rates. STUDY DESIGN: Twenty-seven clinical and 43 placental phenotypes were retrospectively compared in 4617 third-trimester births: 1332 preterm pregnancies (28-33 weeks' gestation), 1066 late preterm pregnancies (34-36 weeks' gestation), 940 near-term pregnancies (37-38 weeks' gestation), and 1279 term pregnancies (≥39 weeks' gestation). RESULTS: Acute inflammatory pattern of placental injury was seen mostly at both gestational sides of the third trimester; the clinical conditions linked to in utero hypoxia (preeclampsia, diabetes mellitus, fetal growth restriction) and their placental associations (atherosis, membrane chorionic microcysts, chorangiosis, intervillous thrombi) were associated statistically significantly with mid third trimester. Acute fetal distress (abnormal fetal heart tracing and clinical and histologic meconium) were increasing with gestational age and were statistically significantly most common in full-term pregnancies. CONCLUSION: Differences in placental pathologic condition among the 4 subgroups of third-trimester pregnancy not only challenge the use of an arbitrary cutoff point of 37 weeks' gestation that separates the preterm birth and term birth but also further support separation of late preterm births from preterm births and term births from near-term births. Based on placental pathologic condition, chronic uteroplacental malperfusion is the dominating etiopathogenetic factor in the mid third trimester (late preterm and near-term births), and acute fetal distress is the factor in full-term births. This obscures relative frequencies of perinatal death and management modalities in the third trimester.

Clinicoplacental phenotypes vary with gestational age: an analysis by classical and clustering methods.

OBJECTIVE: As the patterns and frequency of maternal and clinical conditions and outcomes and gross and histological placental features and lesions vary with gestational age at delivery, we aimed to study the impact of these changes on the placental diagnosis, hoping to uncover potential novel clusters of gestational age-associated clinical and pathological diagnoses. DESIGN: Retrospective statistical analysis of clinicoplacental database. POPULATION: We analyzed 28 clinical (maternal and fetal) and 49 gross and microscopic placental variables from 3294 consecutively signed placentas received between 2001 and 2012, divided into three gestational age groups: 16-27 weeks, 697 cases; 28-36 weeks, 1365 cases; and 37+ weeks, in all 1232 cases. METHODS: Classical statistics by chi-squared and Fischer's tests, and the Ward agglomerative hierarchical clustering and multidimensional scaling techniques, were used. RESULTS: The placental phenotypes clustered statistically significantly with severe preeclampsia in the second trimester; preterm premature rupture of membranes, placental abruption, and fetal growth restriction in the whole third trimester; and abnormally invasive placenta, thick meconium, maternal diabetes mellitus, and substance abuse in term pregnancies. CONCLUSIONS: The applied statistical analyses made it possible to simultaneously compare the strength of clinicoplacental associations separately in three pregnancy intervals. Placental clinicopathological associations are strongest for the second trimester, i.e. severe preeclampsia and preterm ascending infection-related conditions, but were not significant for other pregnancy complications such as mild preeclampsia, chronic hypertension, diabetes mellitus, or umbilical cord compromise.