Intertwin Membrane Perforation and Umbilical Cord Entanglement after Laser Surgery for Twin-Twin Transfusion Syndrome: Prevalence, Risk Factors, and Outcome.

INTRODUCTION: Perforation of the intertwin membrane can occur as a complication of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Data on the occurrence and the risk of subsequent cord entanglement are limited. The objective of this study was to assess the prevalence, risk factors and outcome of intertwin membrane perforation, and cord entanglement after laser surgery for TTTS. METHODS: In this multicenter retrospective study, we included all TTTS pregnancies treated with laser surgery in two fetal therapy centers, Shanghai (China) and Leiden (the Netherlands) between 2002 and 2020. We evaluated the occurrence of intertwin membrane perforation and cord entanglement after laser, based on routine fortnightly ultrasound examination and investigated the risk factors and the association with adverse short- and long-term outcomes. RESULTS: Perforation of the intertwin membrane occurred in 118 (16%) of the 761 TTTS pregnancies treated with laser surgery and was followed by cord entanglement in 21% (25/118). Perforation of the intertwin membrane was associated with higher laser power settings, 45.8 Watt versus 42.2 Watt (p = 0.029) and a second fetal surgery procedure 17% versus 6% (p < 0.001). The group with intertwin membrane perforation had a higher rate of caesarean section (77% vs. 31%, p < 0.001) and a lower gestational age at birth (30.7 vs. 33.3 weeks of gestation, p < 0.001) compared to the group with an intact intertwin membrane. Severe cerebral injury occurred more often in the group with intertwin membrane perforation, 9% (17/185) versus 5% (42/930), respectively (p = 0.019). Neurodevelopmental outcome at 2 years of age was similar between the groups with and without perforation of the intertwin membrane and between the subgroups with and without cord entanglement. CONCLUSION: Perforation of the intertwin membrane after laser occurred in 16% of TTTS cases treated with laser and led to cord entanglement in at least 1 in 5 cases. Intertwin membrane perforation was associated with a lower gestational age at birth and a higher rate of severe cerebral injury in surviving neonates.

Alterations in maternal plasma exosomal miRNAs revealed selective material exchange between maternal circulation and placenta.

AIM: Exosomes have emerged as important regulators in the communication between maternal peripheral blood and placenta. We aimed to compare maternal plasma exosomal miRNAs profile between healthy pregnant and nonpregnant women, screen for differential expressed miRNAs and their potential regulatory role during pregnancy. METHODS: We isolated exosomes from plasma of mid-trimester, last trimester, and nonpregnant women (n = 6 each group), analyzed the miRNA profile using next-generation sequencing. RESULTS: Several miRNA clusters were expressed in plasma exosomes, such as C19MC, C14MC, and let-7 family, miRNAs in each cluster may have synergistic effect during pregnancy. We assumed maternal circulating exosomal miRNA could be transported into placenta or selectively uptook by placenta, which was consistent with the fact that many pregnancy-associated or placenta highly expressed miRNAs reduced in exosomes during pregnancy. Some exosomal miRNAs were mainly secreted by the placenta, which could act as markers that reflect changes in the function and microenvironment of the placenta. CONCLUSIONS: Exosomal miRNAs are associated with placenta development and have potential as molecular markers.

Placental Abruption after Fetoscopic Laser Surgery in Twin-Twin Transfusion Syndrome: The Role of the Solomon Technique.

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) is a complication in monochorionic twin pregnancies which is preferably treated with fetoscopic laser surgery. A few small studies suggested a possible association between the Solomon laser technique and placental abruption. METHODS: The objective of this study is to compare the rate of and to explore potential risk factors for placental abruption in TTTS treated with fetoscopic laser surgery according to the Selective and Solomon laser technique. We conducted a large retrospective cohort study of consecutive TTTS-cases treated with fetoscopic laser surgery in Shanghai, China, and Leiden, The Netherlands treated with either the Selective laser technique (Selective group) or Solomon laser technique (Solomon group). RESULTS: The rate of placental abruption in the Selective group versus the Solomon group was 1.7% (5/289) and 3.4% (15/441), respectively (p = 0.184). No risk factors for placental abruption were identified. Placental abruption was associated with lower gestational age at birth (p = 0.003) and severe cerebral injury (p = 0.003). CONCLUSION: The prevalence of placental abruption in TTTS after fetoscopic laser surgery is low, although it appears higher than in the overall population. Placental abruption is associated with a lower gestational age at birth, which is associated with severe cerebral injury. The rate of placental abruption was not significantly increased with the use of the Solomon technique. Continued research of placental abruption in TTTS is necessary to determine why the rate is higher than in the overall population.

Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway.

One of the dominant effects of glucocorticoids in triggering parturition in certain animal species is to drive the placental conversion of progesterone to estrogen. However, in the human placenta, estrogen is formed using dehydroepiandrosterone from the fetal adrenal glands rather than progesterone as precursor. Although aromatization of dehydroepiandrosterone is crucial in estrogen synthesis in human placenta, it is not known whether glucocorticoids affect aromatase expression. Human term placental syncytiotrophoblasts were used to examine the effect of cortisol on aromatase expression. The signaling pathway and transcription factors involved were identified in this study. Results showed that cortisol induced aromatase expression in a concentration-dependent manner, which was mediated indirectly by glucocorticoid receptor and required the participation of other proteins. The induction of aromatase by cortisol could be blocked by either specificity protein 1 (Sp1) antagonist mithramycin or knockdown of Sp1 expression. The induction of aromatase and Sp1 by cortisol could be prevented by inhibitors of the cAMP pathway, whereas activators of the cAMP pathway induced Sp1 and aromatase expression as well as Sp1 binding to aromatase promoter. Concomitantly, cortisol treatment and activation of the cAMP pathway led to increased acetylation and decreased methylation of histone 3 at the aromatase promoter. In conclusion, cortisol stimulates aromatase expression through the cAMP/Sp1 pathway in human placental syncytiotrophoblasts. These findings reveal a novel role of cortisol in increasing the local level of estrogen within the placenta that would help transform the myometrium to a contractile state, thereby contributing to a cascade of events leading to human parturition.