Svetlana Shapiro

Placental markers of twin-to-twin transfusion syndrome in diamniotic–monochorionic twins: A morphometric analysis of deep artery-to-vein anastomoses

Twin-to-twin transfusion syndrome (TTTS) is a multifactorial disorder that develops in 9-15% of diamniotic-monochorionic twin gestations. While the pathogenesis of TTTS remains poorly understood, unbalanced deep artery-to-vein (AV) anastomoses have traditionally been implicated in the gradual shift of blood from donor to recipient. The aim of this study was to define the placental markers of twin-to-twin transfusion syndrome, with special emphasis on the deep AV anastomoses. A prospective cohort of 284 consecutive diamniotic/monochorionic twin placentas was examined at Women and Infants Hospital between 2001 and 2008. Following exclusion of monoamniotic, multiple, disrupted and laser-treated placentas, 218 twin placentas (21 TTTS and 197 non-TTTS controls) formed the subject of this study. Placentas were injected with color-coded dyes. Anatomic characteristics and choriovascular anastomotic patterns of TTTS placentas were compared with non-TTTS controls. The TTTS placentas showed significantly higher frequencies of velamentous cord insertion, magistral vascular distribution patterns, uneven placental sharing, absence of AA anastomoses and presence of VV anastomoses. Deep AV anastomoses were identified in >or=95% of TTTS and non-TTTS placentas and were overall more abundant than previously reported. The total and net numbers of AV anastomoses were similar in both groups. However, the net cross-sectional area of AV anastomoses, which also takes into account the caliber of the vessels, was significantly smaller in TTTS placentas. There was no correlation between the direction of the AV imbalance and the twin donor/recipient status. In conclusion, TTTS has distinct placental characteristics, warranting their routine inclusion in the diamniotic-monochorionic placental pathology report. Our findings suggest imbalance of AV anastomoses is not required for the development for TTTS, although their presence, whether balanced or unbalanced, may contribute to the creation or perpetuation of the syndrome. Elucidation of the role of the various placental determinants in diamniotic-monochorionic twin gestations may lead to further refinement of therapeutic strategies.

Placental intravascular organisms: A case report

Ascending amniotic fluid bacterial infection is a cause of perinatal morbidity and mortality. A diagnosis of amniotic cavity infection can be inferred by documenting maternal (acute chorioamnionitis) and/or fetal (chorionic plate vasculitis; umbilical vasculitis/funisitis) inflammatory response. A definitive diagnosis of intrauterine/neonatal sepsis as a cause of stillbirth requires positive blood cultures obtained at postmortem examination. However, if postmortem examination is not performed, acute chorioamnionitis with/without fetal inflammatory response cannot be classified as a cause of demise. We present a case of intrauterine demise associated with acute chorioamnionitis, villitis, and intervillositis of the placenta. Although postmortem examination was denied, a conclusive diagnosis of intrauterine sepsis could be rendered by demonstration of gram-positive cocci within fetal vessels of umbilical cord, chorionic plate, and stem villi. This report highlights the importance of identification of placental intravascular organisms as unequivocal evidence of fetal sepsis, especially in cases where cultures cannot be obtained.

Correlation between cord insertion type and chorionic villus vascularization of the co-twin in diamniotic–monochorionic twin pregnancies

BACKGROUND Recent evidence suggests that cord insertion type of one twin correlates with chorionic plate vascularization of the monochorionic co-twin. Specifically, for twins with paracentral cords, chorionic plate vascularization is significantly greater when the co-twin has a velamentous, rather than paracentral cord insertion. AIMS To determine whether this correlation between cord insertion type and vascularization of the co-twin also extends to the deeper chorionic villus tree. STUDY DESIGN Morphometric analysis of chorionic villus vascularization in CD31-immunostained sections of a retrospective cohort of gestational age-matched third trimester monochorionic placentas with discordant paracentral/velamentous (PC/V) or concordant paracentral/paracentral (PC/PC) cord insertions. OUTCOME MEASURES Vascular numerical density (number of vascular profiles per unit villus stromal area) of intermediate villi (>80 μm diameter) and terminal villi (<80 μm). RESULTS For twins with paracentral cord insertion, the vascular numerical density of intermediate villi was significantly higher for twins in a discordant PC/V relationship than for those in a concordant PC/PC relationship (P<0.05), thus replicating previous findings in superficial chorionic vessels. For terminal villi, in contrast, the vascular numerical density of twins with paracentral cords in a PC/V combination was significantly lower than of those in a PC/PC combination, and similar to that of their co-twins with velamentous cord insertion. CONCLUSIONS Early placental angiogenesis in monochorionic twin gestations may be influenced by implantation and cord localization of the co-twin. The regulation of terminal villus angiogenesis appears to be dissociated from more proximal villus angiogenesis and independent of cord insertion of the co-twin.

Veno-venous anastomoses in twin-twin transfusion syndrome: A multicenter study.

INTRODUCTION The aim of this study is to evaluate the prevalence of veno-venous (VV) anastomoses in a large cohort of monochorionic (MC) twin placentas with twin-twin transfusion syndrome (TTTS) compared to a control group of MC placentas without TTTS. METHODS All TTTS placentas not treated with fetoscopic laser surgery (TTTS group) and examined at five international fetal therapy centers were included in this study and compared with a control group of MC placentas without TTTS (non-TTTS group). MC placentas were routinely injected with colored dye. We recorded the presence of VV and arterio-arterial (AA) anastomoses. RESULTS A total of 414 MC placentas were included in this study (TTTS group, n = 106; non-TTTS group, n = 308). The prevalence of VV anastomoses was significantly higher in the TTTS group than in the non-TTTS group, 36% (38/106) and 25% (78/308), respectively (p = .04; odds ratio (OR) 1.65; 95% confidence interval (CI): 1.03-2.64). In the subgroup of MC placentas without AA anastomoses, the prevalence of VV anastomoses in the TTTS group and non-TTTS group was 32% (18/57) and 8% (2/25), respectively (p = .03; OR: 5.31; 95% CI: 1.13-24.98). DISCUSSION VV anastomoses are detected more frequently in TTTS placentas than in MC placentas without TTTS and may thus play a role in the development of TTTS.

Placental endoglin levels in diamniotic-monochorionic twin gestations: Correlation with clinical and placental characteristics

OBJECTIVE While endoglin has been implicated in the pathogenesis of various complications in singleton pregnancies, its potential contribution to complications of monochorionic twinning remains largely undetermined. The aim of this study was to determine the correlation between relevant clinical and pathological variables and placental endoglin levels in diamniotic-monochorionic twin pregnancies. METHODS Endoglin expression was studied by immunohistochemistry and Western blot in a prospective cohort of 68 non-TTTS and 7 TTTS monochorionic twin placentas. Placental endoglin levels were correlated with clinical and placental characteristics associated with twin-to-twin transfusion syndrome (TTTS) and selective growth restriction, including birth weight discordance, uneven placental sharing, peripheral cord insertion and choriovascular anatomy. RESULTS In non-TTTS gestations discordant for these criteria, placental endoglin levels were significantly higher for the twin with smaller birth weight, intrauterine growth restriction, and/or abnormal ultrasound Doppler studies than for the more normal co-twin. Similarly, placental endoglin levels were significantly higher in the placental territory with smaller share and/or peripheral cord insertion in cases discordant for these placental characteristics. In TTTS gestations, placental endoglin levels tended to be higher for donor twins than for recipients. There was no correlation between endoglin levels and superficial choriovascular anastomoses. CONCLUSIONS While the exact functional implications remain to be determined, our findings suggest a strong correlation between unbalanced placental endoglin levels and intertwin growth discordance in monochorionic twins.