Cases Of Twin-twin Transfusion Syndrome Research Articles

Elevated middle cerebral artery peak systolic velocity and risk of death in donor twin affected by twin-twin transfusion syndrome but not twin anemia-polycythemia sequence.

To determine the association between elevated (> 1.5 multiples of the median (MoM)) middle cerebral artery (MCA) peak systolic velocity (PSV) and fetal demise of the donor twin in pregnancies complicated by twin-twin transfusion syndrome (TTTS) in the absence of twin anemia-polycythemia sequence (TAPS). Secondary objectives were to evaluate if donor or recipient MCA-PSV is associated with a risk for their corresponding fetal death, and to compare the proportion of donor fetuses with low MCA pulsatility index (PI) among donor twins with high MCA-PSV and those with normal MCA-PSV to evaluate the contribution of blood-flow redistribution to the fetal brain in donor twins with high MCA-PSV. This prospective cohort study included TTTS cases that underwent laser surgery between 2011 and 2022 at a single center. TAPS cases were excluded from the study. Multivariable and Poisson regression analysis were performed to explore the association between isolated elevated donor MCA-PSV and fetal demise, adjusted for TTTS stage, selective fetal growth restriction (sFGR) and other confounders. Of 660 TTTS cases, donor MCA-PSV was not recorded in 48 (7.3%) cases. Of the remaining 612 patients, nine (1.5%) were lost to follow-up and 96 TAPS cases were excluded; thus, 507 cases were included in the study. High donor MCA-PSV was seen in 6.5% (33/507) of cases and was an independent risk factor for donor fetal demise (adjusted relative risk (aRR), 4.52 (95% CI, 2.72-7.50)), after adjusting for confounders. Regression analysis restricted to each Quintero TTTS stage demonstrated that high donor MCA-PSV was an independent risk factor for fetal demise of the donor in Quintero Stage II (aRR, 14.21 (95% CI, 1.09-186.2)) and Quintero Stage III (aRR, 3.41 (95% CI, 1.82-6.41)). Donor MCA-PSV in MoM was associated with fetal demise of the donor (area under the receiver-operating-characteristics curve (AUC), 0.69; P < 0.001), but recipient MCA-PSV in MoM was not associated with fetal demise of the recipient (AUC, 0.54; P = 0.44). A higher proportion of donor twins in the group with high MCA-PSV had a low MCA-PI compared to the group with normal MCA-PSV (33.3% vs 15.5%; P = 0.016). Elevated donor MCA-PSV without TAPS prior to laser surgery for TTTS is associated with a 4-fold increased risk for donor fetal demise, adjusted for sFGR, TTTS stage and other confounders. Doppler evaluation of donor MCA-PSV prior to laser surgery may help stratify TTTS staging to evaluate the risk of donor fetal demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

SFM Fetal Therapy Practice Guidelines: Bipolar Cord Coagulation

AbstractBipolar cord coagulation is modality available for the treatment of monochorionic diamniotic twins with any one of the following indications: discordant anomalous fetus, severe selective Intrauterine growth restriction (IUGR) (type 2 and type 3) in very preterm and premature fetuses, and selected cases of twin-twin transfusion syndrome when LASER photocoagulation is not feasible. Twin reversed arterial perfusion sequence with polyhydramnios and cardiac overload in pump twin, Multifetal reduction involving MCDA pair.

Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome

Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two distinct clusters of disease defined by levels of glucose metabolites, amino acids, urea, and redox status. Our results suggest that the human fetal heart can adapt to hemodynamic stress by modulating its glucose metabolism and identify potential differences in the ability of individual fetuses to respond to cardiovascular stress.

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.

Fetal Doppler in monochorionic pregnancies complicated by twin-to-twin transfusion syndrome and selective in utero growth restriction

BackgroundMonochorionic (MC) twin pregnancies may be complicated by placental pathologies that impact fetal cardiac function, such as twin-twin transfusion syndrome (TTTS) and selective intrauterine growth-restriction (sIUGR). In the TTTS, the unbalanced blood flow through placental anastomoses lead a recipient volume overload, hypertension and hypertrophic cardiomyopathy and the donor twin experiences hypovolemia and hypertension due to increased placental resistance and poor renal perfusion. When MC pregnancies were complicated by sIUGR, the increase of placental resistances lead to complex fetal compensatory mechanisms with redistribution of cardiac output to vital organs. Increased placental vascular resistances, hypoxia and hemodynamic compensation mechanisms lead to higher pre and/or afterload for both ventricles, right cardiac failure and eventually left cardiac failure observed just before fetal death. ObjectivesThe purpose of this study was to describe the anomalies of umbilical, ductal and aortic isthmic Doppler as well as left and right myocardial performance index (MPI) across various clinical phenotypes of MC twin pregnancies, uncomplicated or complicated by TTTS or sIUGR, in order to help differentiating these conditions and to improve the understanding of TTTS and sIUGR pathophysiology. Study designAortic isthmic systolic index (ISI), umbilical artery pulsatility index (UAPI), ductus venosus pulsatility index (DVPI), and MPI were studied in uncomplicated MC twins (control group) and cases of sIUGR or TTTS. ResultsThe measurements were obtained in 113 pregnancies (24 uncomplicated, 22 sIUGR, 51 TTTS). In comparison with controls, the sIUGR smaller twin sets had lower ISI and higher UAPI, and the larger twin had higher ISI. The TTTS donor and recipient had lower ISI, higher UAPI and DVPI. Compared to the co-twin, the ISI values were lower in the sIUGR smaller twin and the TTTS donor had lower ISI and MPI. Comparing TTTS and sIUGR, the recipient had higher DVPI and MPI than the sIUGR larger twin. ConclusionsThe Doppler anomalies observed in the smaller twin reflected increased placental blood flow resistance, presumably due to abnormal feto-fetal transfusion in TTTS and to unequal placental sharing in sIUGR. Early hemodynamic changes suggestive of cardiac overload in the recipient twin may help to differentiate TTTS and sIUGR.

Effect of Gestational Age at Fetoscopic Laser Photocoagulation on Perinatal Outcomes for Patients with Twin–Twin Transfusion Syndrome

The aim of this study was to evaluate the effect of gestational age (GA) at the time of fetoscopic laser photocoagulation (FLP) for severe twin-twin transfusion syndrome (TTTS) on perinatal outcomes in a single center in Taiwan. Severe TTTS was defined as a diagnosis of TTTS before a GA of 26 weeks. Consecutive cases of severe TTTS treated at our hospital with FLP between October 2005 and September 2022 were included. The evaluated perinatal outcomes were preterm premature rupture of membranes (PPROM) within 21 days of FLP, survival 28 days after delivery, GA at delivery, and neonatal brain sonographic imaging findings within 1 month of delivery. We included 197 severe TTTS cases; the mean GA at the time of FLP was 20.6 weeks. After the cases were divided into cases of FLP at early (below 20 weeks) and late GAs (more than 20 weeks), the early-GA group was discovered to be associated with a deeper maximum vertical pocket in the recipient twin, a higher rate of PPROM development within 21 days of FLP, and lower rates of survival of one or both twins. In the cases of stage I TTTS, the rate of PPROM within 21 days of FLP was higher in the group that underwent FLP at an early GA than in the group that underwent FLP at a late GA (50% (3/6) vs. 0% (0/24), respectively, p = 0.005). Logistic regression analysis revealed that the GA at the time of FLP and the cervical length before FLP is implemented are significantly associated with the survival of one twin and the incidence of PPROM development within 21 days of FLP. The GA at the time of FLP, the cervical length before FLP, and TTTS being stage III TTTS were associated with the survival of both twins after FLP. Neonatal brain image anomalies were associated with GA at delivery. FLP being performed at an earlier GA is a risk factor for lower fetal survival and PPROM development within 21 days of FLP in cases of severe TTTS. Delaying FLP for cases involving stage I TTTS diagnosed at an early GA without risk factors, such as maternal symptoms, cardiac overload in the recipient twin, or a short cervical length, may be considered, but whether delaying FLP would improve surgical outcomes and, if so, how long the delay should be may need further trials to answer.

Impact of Selective Fetal Growth Restriction on Laser Therapy Outcomes in Twin-Twin Transfusion Syndrome

Introduction: The aim of this study was to determine if outcomes of fetoscopic laser photocoagulation in isolated twin-twin transfusion syndrome (TTTS) differ from TTTS with concomitant selective fetal growth restriction (sFGR). Methods: This is a retrospective cohort study of all cases of TTTS treated at the CHU Sainte-Justine between February 2006 and January 2020. Data were collected from maternal, obstetrical, and neonatal chart review. Results: A total of 149 patients were included in our study. Forty-seven patients (31.5%) had a pregnancy complicated by TTTS and sFGR. Mean gestational age at diagnosis and at treatment was 20+4 weeks and 20+6 weeks for TTTS alone, and 20+5 weeks and 21+2 weeks with concomitant sFGR. The presence of concomitant sFGR negatively impacted survival. Double survival in the TTTS + sFGR was 48.9% (23/47) versus 68.6% (70/102) in the TTTS-only group (p = 0.021). Fetal donor survival was 59.6% (28/47) in the TTTS + sFGR group and 84.3% (86/102) in the TTTS-only group (p = 0.001). However, the survival of at least one twin did not differ between the two groups: 93.6% (44/47) in the TTTS + sFGR group versus 92.2% (94/102) in the TTTS-only group (p = 0.751). The presence of type 2–3 sFGR (OR = 0.56; 95% CI 0.32–0.96, p = 0.033) and gestational age at laser therapy (OR = 1.17; 95% CI 1.01 = 1.36, p = 0.036) were independently associated with dual survival. Conclusion: sFGR is independently associated with decreased double survivorship at the expense of the donor in TTTS undergoing laser therapy. Type 2 or 3 sFGR and early gestational age at treatment are especially at risk. A larger cohort is needed to validate our results.

Impact of middle cerebral artery pulsatility index on donor survival in twin-twin transfusion syndrome.

To assess outcomes in twin-twin transfusion syndrome (TTTS) according to middle cerebral artery pulsatility index (MCA-PI) prior to fetoscopic laser photocoagulation (FLPC) surgery. A retrospective cohort analysis of monochorionic-twin pregnancies complicated by TTTS who underwent FLPC at two fetal centers (2012-2021). The cohort was stratified according to abnormal MCA-PI of the donor twin, defined as below fifth centile for gestational age. Abnormal MCA-PI of the donor twin was detected in 46 (17.7%) cases compared to 213 (83.3%) controls with no such abnormality. The abnormal PI group presented with higher rates of sFGR (56.5% vs. 36.8% in controls, p=0.014) and lower donor survival rates within 48h after FLPC (73.9 vs. 86.8%, p=0.029). Donor twin survival rates at the time of delivery and 30days after birth were lower in the abnormal MCA-PI. Multivariate logistic regression analysis controlling for sFGR and MCA-PI <fifth centile demonstrated the latter to be independently associated with lower survival rates at the time of delivery and 30days after birth [OR=0.497 95%CI (0.250-0.986) p=0.045, and OR=0.499 95%CI (0.252-0.986), p=0.046, respectively]. Recipient's survival rates did not differ between the groups. Donor survival at the time of delivery and 30days after birth was lower in TTTS cases with MCA-PI<fifth centile for gestational age prior to laser surgery. This parameter may be considered when evaluating prognosis for TTTS.

Abstract 10875: Metabolic Reprogramming of the Failing Fetal Heart in Twin-Twin Transfusion Syndrome

Adult heart failure is associated with reactivation of the fetal metabolic program, including impaired mitochondrial oxidative phosphorylation and a shift toward glycolysis. In the fetus, the metabolic response to cardiac stress is less clear. We used twin-twin transfusion syndrome (TTTS) as a model to uncover metabolic adaptations of the fetus to cardiovascular stress. TTTS is a unique complication that occurs in monochorionic-diamniotic twins (one placenta, two amniotic sacs) when unequal blood flow between twins within the shared placenta is the set up for donor-recipient physiology (Fig 1a). This circulatory imbalance is detected by sonographic signs of donor hypovolemia and recipient hypervolemia. We analyzed second trimester amniotic fluid to identify alterations in metabolism of TTTS recipient twins (n=22) vs. singleton controls (n=10) using untargeted metabolomics (LC/MS). All TTTS cases were severe (stage III; abnormal Dopplers indicating increased afterload and/or right heart failure). Due to dilution of amniotic fluid molecules in TTTS, data for each sample was normalized to protein concentration. Evaluation of differential metabolites in TTTS cases revealed two distinct clusters of disease (Fig. 1b). Compared with TTTS cluster 1 and controls, cluster 2 showed significantly increased lactate and alanine production, and evidence of redox stress (Fig. 1c). No differences in clinical characteristics or outcomes were observed between TTTS cluster 1 vs. 2 (maternal age, gestational age, fetal sex, disease severity, preterm birth, and perinatal death). Our findings reveal subclinical heterogeneity of stage III TTTS and suggest that some fetuses undergo metabolic reprogramming under conditions of cardiac stress, shifting even further toward energy-efficient glucose utilization. These differences in fetal response may represent different points along the same spectrum vs. inherent differences in the ability of fetuses to adapt to stress.

Effect of Fetoscopic Laser Photocoagulation on Fetal Growth and Placental Perfusion in Twin-Twin Transfusion Syndrome.

Objective: To investigate the fetal growth pattern after fetoscopic laser photocoagulation (FLP) in twin-twin transfusion syndrome (TTTS) and the effect of FLP on placental perfusion and intrauterine growth restriction (IUGR) incidence. Methods: TTTS cases with a live delivery of both twins at least 28 days after FLP and with a neonatal follow-up at our hospital at least 60 days after delivery were included. The biometric data obtained before FLP (based on ultrasound); time point M1), upon birth (M2), and at neonatal follow-up (M3) were analyzed. The body weight discordance (BWD) was defined as (estimated fetal weight [body weight] of the recipient twin − estimated fetal weight [body weight] of the donor twin)/(estimated fetal weight [body weight] of the recipient twin) × 100%. Total weight percentile (TWP) was defined as the donor + recipient twin weight percentile; the TWP indirectly reflected the total placental perfusion. Results: the BWDs decreased from M1 to M2 to M3 (24.6, 15.9, and 5.1, respectively, p < 0.001, repeated measurements). The weight percentiles of recipient twins decreased after FLP, that is, from M1 to M2 (53.4% vs. 33.6%, respectively, p < 0.001, least significant difference [LSD] test). However, the weight percentiles of donor twins increased after delivery, that is, from M2 to M3 (13.2% vs. 26.2%, respectively, p < 0.001, LSD test). Moreover, the TWPs decreased after FLP, that is, from M1 to M2 (66.2% vs. 46.8%, respectively, p = 0.002, LSD test) and increased after delivery, that is, from M2 to M3 (46.8% vs. 63.2%, respectively, p = 0.024, LSD test). The IUGR incidences in donor twins were significantly lower after FLP (77.4% vs. 56.6%, respectively, p = 0.019, McNemar test) and further decreased after delivery (56.6% vs. 37.7%, respectively, p = 0.041, McNemar Test); however, no significant difference was observed in recipient twins’ IUGR incidences among M1, M2, and M3. The donor twin had catch- up growth in body weight, height, and head circumference after delivery, and the recipient twin had catch-up growth in only body height after delivery. Conclusions: the BWD decreased after FLP in fetuses with TTTS mainly because of the decreased weight percentiles of recipient twins. Moreover, it further decreased after delivery mainly because of the increased weight percentiles of donor twins. FLP not only decreased placental perfusion but also improved the TTTS prognosis because of reduced BWD and donor twin IUGR incidence.

Optimizing Fetal Outcomes in Twin-Twin-Transfusion Syndrome using Serial Amnioreduction in Resource-Constrained Unit: A Case Report

Background: Twin-twin transfusion syndrome is an important complication of monochorionic placentation in twin pregnancy. The management of this condition in Nigeria and many other developing countries has always been “watchful expectancy” with attendant high perinatal morbidity and mortality. Amnioreduction is a less demanding treatment option compared with fetoscopic laser coagulation management option in terms of cost and expertise, but has not been reported from any unit in Nigeria. Case Presentation: A 28-year-old gravid 2 para 1+0, 1 alive, carrying twin pregnancy was referred at 22 weeks gestation with complaint of mild discomfort due to sudden rapid enlargement of the abdomen. Physical examination and ultrasound scan assessment confirm Quintero stage II Twin-twin transfusion syndrome and she underwent serial amnioreduction at 24, 28 and 31 weeks of gestation with satisfactory outcomes. She had caesarean section at 33 weeks due to an acute episode of severe maternal discomfort and was delivered of 2 live female babies. There were no adverse perinatal events. Conclusion: This case presented demonstrates the role of amnioreduction in the management of carefully selected cases of twin-twin transfusion syndrome and further encouraged its utilization. in resource-constrained units instead of ‘watchful expectancy’ and in the absence of fetoscopic laser photocoagulation

The Efficacy of Fetoscopic Laser Surgery in Twin-Twin Transfusion Syndrome: A Preliminary Vietnamese Study.

Twin-twin transfusion syndrome (TTTS) is a severe prenatal complication of monochorionic diamniotic twins (MCDA). If left untreated, TTTS is associated with a high risk of neonatal death and neurological complications. Various treatment methods for TTTS have been proposed, but fetoscopic laser surgery (FLS) is currently the primary treatment for TTTS in global fetal medicine centers. The objective of this study was to evaluate the outcome of TTTS following FLS treatment at Hanoi Obstetrics and Gynecology Hospital (HOGH), a new fetal medicine center in Vietnam. A prospective study of a series of 33 consecutive TTTS cases prior to 26 weeks of gestation subjected to FLS at HOGH in Vie-tnam between September 2019 to July 2021. Neonates were monitored for at least six months after birth. The survival rate of at least one fetus reached 84.85%. No short-term neurological complications have been reported upon follow-up of the newborn up to six months after birth. There were three stillbirth cases (9.09%), one case of preterm ruptured membra-nes (PROM) (3.03%) after seven days of surgery and three cases of recurrent TTTS after surgery using the Solomon technique (25%). No maternal complications were observed. The mean gestational age at birth was 33.76 ± 4.52 weeks, with a mean interval of 12.24 ± 6.67 weeks between intervention and delivery. Nine cases (30%) were born prematurely before 32 weeks. Additionally, 60% of recipients and nearly 90% of donors weighed less than 2500 grams. FLS leads to high survival rates for fetuses with TTTS. FLS seems to be an effective therapeutic option for TTTS before 26 weeks of gestation.

OC17.04: Twin–twin transfusion syndrome and COVID‐19: impact on diagnosis, referral and eligibility for fetoscopic laser therapy and outcomes

To assess the clinical impact of the coronavirus disease 2019 (COVID- 19) pandemic on pregnancies complicated with Twin–twin transfusion syndrome (TTTS). Retrospective cohort of pregnancies with TTTS evaluated in our fetal surgery centre at Queretaro, Mexico for possible surgical fetoscopy. Maternal-fetal characteristics and perinatal outcomes of cases evaluated during the first year of the COVID-19 pandemic declaration (03/11/2020 - 03/10/2021) were retrospectively compared with those cases assessed during the same period in the previous year. 109 TTTS cases were evaluated, 54 during the COVID-19 pandemic and 55 in the previous year. In the former group, a higher proportion of cases with fetal surveillance interval longer than 2 weeks (70.4 vs. 47.3%, p = 0.01), TTTS complications precluding laser therapy such as IUFD, PPROM, or cervical dilatation with prolapsed amniotic membranes (18.5 vs. 1.8%, p < 0.01), advanced TTTS (53.7 vs 36.4%, p = 0.07), preoperative short cervix (25.9 vs 10.9%, p < 0.05), and lower overall perinatal survival (56.9 vs. 80.0%, p = 0.01 of at least one twin; and 39.2 vs 56.4%, p = 0.08 of both twins) were observed. A significantly lower number of cases were selected for fetoscopic laser therapy during the pandemic period (75.9 vs 92.7%, p = 0.01); similar postoperative outcomes were observed both study groups. In pregnancies with TTTS, the COVID-19 pandemic has shown an adverse impact involving suboptimal fetal surveillance, advanced stage at diagnosis, poorer survival rates, and higher number of complications that preclude fetosopic laser therapy. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Differentiation between TTTS Stages I vs II and III vs IV does not affect probability of double survival after laser therapy

To compare the perinatal outcome of monochorionic twin pregnancies with twin-twin transfusion syndrome (TTTS), according to the disease severity, defined using Quintero staging, after treatment with fetoscopic laser surgery. This was a single-center study of 1020 consecutive cases with severe TTTS, which were treated with fetoscopic laser surgery. During the study period from January 1995 to March 2013, the participants were included at a mean ± SD gestational age of 20.8 ± 2.2 weeks. Perinatal survival analysis, including the rates of double survival and survival of at least one fetus, was undertaken according to the Quintero staging system. For blockwise comparisons of data, the whole population was divided into five chronologically consecutive study subgroups of 200 patients in each of the first four subgroups and 220 in the last one. For the entire study population with known outcome (n = 1019), the rate of pregnancy with double fetal survival was 69.0% (127/184) in Stage-I, 71.4% (257/360) in Stage-II, 55.4% (236/426) in Stage-III and 51.0% (25/49) in Stage-IV TTTS cases. At least one twin survived in 91.3% (168/184) of pregnancies with Stage-I, 89.7% (323/360) of those with Stage-II, 83.1% (354/426) of those with Stage-III and 77.6% (38/49) of those with Stage-IV TTTS. The rates of double survival and survival of at least one fetus were both significantly higher in Stage-II TTTS compared with those in Stage-III TTTS cases (P < 0.001 and P = 0.011, respectively). Survival rates between pregnancies with Stage-I vs Stage-II TTTS and between those with Stage-III vs Stage-IV TTTS were not significantly different. Therefore, we combined pregnancies with Stage-I or Stage-II TTTS, and those with Stage-III or Stage-IV TTTS. The double survival rate was 70.6% (384/544) in combined Stage-I and Stage-II vs 54.9% (261/475) in combined Stage-III and Stage-IV TTTS cases (P < 0.001). At least one twin survived in 90.3% (491/544) of pregnancies with Stage-I or Stage-II TTTS vs 82.5% (392/475) in those with Stage-III or Stage-IV TTTS (P < 0.001). The double survival rate increased between the first and the last consecutive study subgroups from 59.8% (55/92) to 75.0% (96/128) (adjusted odds ratio (aOR)linear trend , 1.26 (95% CI, 1.01-1.56); P = 0.037) in pregnancies with Stage-I or Stage-II TTTS and from 41.7% (45/108) to 62.0% (57/92) (aORlinear trend , 1.21 (95% CI, 0.98-1.50); P = 0.082) in those with Stage-III or Stage-IV TTTS. Double survival rate was the lowest for Stage-III cases in which the donor twin was affected by severely abnormal Doppler findings (45.4% (64/141)). Double survival and survival of at least one fetus in monochorionic twin pregnancies with TTTS were related significantly to Quintero stage. However, our data show that the differentiation between Stages I vs II and Stages III vs IV does not have any significant prognostic implication for perinatal survival. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Amniotic fluid microRNA profiles in twin-twin transfusion syndrome with and without severe recipient cardiomyopathy

Twin-twin transfusion syndrome presents many challenges for clinicians, and the optimal means of identifying pregnancies that will benefit most from intervention is controversial. There is currently no clinically available biomarker to detect twin-twin transfusion syndrome or to stratify cases based on the risk factors. microRNAs are small RNAs that regulate gene expression and are biomarkers for various disease processes, including adult and pediatric heart failure. To date, no studies have investigated amniotic fluid microRNAs as biomarkers for disease severity, specifically for severe recipient cardiomyopathy in twin-twin transfusion syndrome cases. This study aimed to assess whether amniotic fluid microRNAs could be useful as biomarkers to identify pregnancies at greatest risk for severe recipient cardiomyopathy associated with twin-twin transfusion syndrome. Amniotic fluid was collected at the time of amnioreduction or selective fetoscopic laser photocoagulation from monochorionic diamniotic twin pregnancies with twin-twin transfusion syndrome at any stage. Fetal echocardiography was performed on all twins before the procedure, and severe cardiomyopathy was defined as a right ventricular myocardial performance index of the recipient fetus of >4 Z-scores. microRNA was extracted from the amniotic fluid samples and analyzed using an array panel assessing 379 microRNAs (TaqMan Open Array, ThermoFisher). Student t tests were performed to determine significant differences in microRNA expression between pregnancies with severe recipient cardiomyopathy and those with preserved cardiac function. A stringent q value of <.0025 was used to determine differential microRNA expression. Random forest plots identified the top 3 microRNAs that separated the 2 groups, and hierarchical cluster analysis was used to determine if these microRNAs properly segregated the samples according to their clinical groups. A total of 14 amniotic fluid samples from pregnancies with twin-twin transfusion syndrome with severe cardiomyopathy were compared with samples from 12 twin-twin transfusion syndrome control cases with preserved cardiac function. A total of 110 microRNAs were identified in the amniotic fluid samples. Twenty microRNAs were differentially expressed, and the top 3 differentiating microRNAs were hsa-miR-200c-3p, hsa-miR-17-5p, and hsa-miR-539-5p. Hierarchical cluster analysis based on these top 3 microRNAs showed a strong ability to differentiate severe cardiomyopathy cases from controls. The top 3 microRNAs were used to investigate the sensitivity and specificity of these microRNAs to differentiate between the 2 groups with a receiver operating characteristic curve demonstrating sensitivity and specificity of 80.8%. All 20 differentially expressed microRNAs were down-regulated in the group with severe cardiomyopathy. Amniotic fluid microRNAs demonstrated differential expression between twin-twin transfusion syndrome recipient fetuses with severe cardiomyopathy and those without and have the potential to be important biomarkers of disease severity in this population.

630 Management of short cervix in twin-twin transfusion syndrome

There is no proven treatment for prevention of preterm birth (PTB) in twin-twin transfusion syndrome (TTTS). Our objective is to compare pregnancy and neonatal outcomes following cervical cerclage to cervical pessary in twin pregnancies complicated by TTTS and short cervix. We conducted a retrospective cohort study of all TTTS cases with a cervical length <30mm at time of evaluation managed in a single center between 2008 – 2018. The TTTS was managed with expectant management, amnioreduction, or selective fetoscopic laser photocoagulation (SFLP). Pregnancies with congenital abnormalities were excluded. Comparisons were made using the Student’s t, Mann-Whitney U, Kruskall-Wallis, and Chi-squared tests as appropriate, with significance reported as p < 0.05. Of 1,340 pregnancies with TTTS evaluated in our center during the study period, 122 had a cervical length <30mm and met inclusion criteria. Cervical cerclage was placed in 79 pregnancies, and cervical pessary in 29. There were no statistical differences in the baseline characteristics between the cerclage and pessary groups. No differences were noted in gestational age at delivery, indications for delivery, pregnancy complications, or survival between the cervical cerclage and pessary groups. In pregnancies complicated by TTTS and short cervix, similar outcomes were noted when treated with cervical cerclage or pessary. A pessary may offer a less invasive treatment option with similar results. Future studies are needed to determine the optimal treatment strategy in these complex pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

987 Preoperative factors associated with favorable outcomes following laser surgery for stage I twin-twin transfusion syndrome

The optimal treatment strategy for Quintero stage I twin-twin transfusion syndrome (TTTS) remains controversial. Identification of preoperative factors predictive of outcomes after laser surgery would be useful for counseling. The study aim was to report perinatal outcomes of stage I TTTS cases treated with laser, and to ascertain the preoperative factors associated with favorable outcomes Monochorionic diamniotic multiple gestations with a gestational age (GA) between 16 and 26 weeks with Quintero Stage I TTTS that underwent laser surgery between 2006 and 2019 were studied retrospectively. A favorable outcome was defined as dual perinatal survival with delivery at or beyond 32 weeks of gestation. Candidate preoperative factors were identified via bivariate analyses, and multivariate regression analyses were performed to determine if these factors were independently associated with the primary composite outcome. Of 124 stage I TTTS patients that underwent laser surgery, the overall mean (SD) GAs at surgery and at delivery were 21.7 (2.1) and 33.0 (3.6) weeks, respectively. Dual survivorship occurred in 109 cases (87.9%), while 99 (79.8%) cases delivered at or beyond 32 gestational weeks. The composite primary outcome occurred in 73 cases (58.9%). On bivariate analysis of preoperative patient characteristics, donor umbilical artery (UA) intermittent absent end diastolic flow (iAEDF), donor UA systolic velocity/diastolic velocity (SD ratio), estimated fetal weight (EFW) percent discordance, and cervical length were associated with the outcome. Multiple logistic regression modeling identified donor UA forward flow (OR 2.38 [95%CI 1.03-5.56], p=0.0433) and cervical length (cm) (1.43 [95%CI 1.02-2.00], p=0.0395) as the only associated factors, yielding a c-statistic of 0.64. With 88% overall dual survivorship and 33 weeks mean GA at delivery, laser surgery for stage I TTTS remains a reasonable option. Robust predictors of favorable outcomes that could be incorporated into preoperative counseling were not identified.

Umbilical Artery Doppler Patterns and Right Ventricular Outflow Abnormalities in Twin-Twin Transfusion Syndrome.

To evaluate the association of abnormal Doppler velocimetric patterns in the umbilical arteries (UAs) and right ventricular outflow tract abnormalities (RVOTAs) in twin- twin transfusion syndrome (TTTS) cases. This retrospective study involved women who had laser surgery for TTTS between January 2012 and May 2018 at a single institution. The prevalence of an RVOTA in either twin was compared among TTTS cases in which both twins had positive end-diastolic flow (EDF) in the UA and those in which either twin had intermittent or persistent absent/reversed UA EDF. Nonparametric tests were used for comparisons. Logistic regression was performed to identify variables associated with an RVOTA in either twin, adjusted for moderate or severe tricuspid regurgitation, right ventricular hypertrophy, right ventricular systolic or diastolic dysfunction, the Quintero stage, and other confounders. P < .05 was considered significant. A total of 126 consecutive TTTS cases were included. Right ventricular outflow tract abnormalities were seen in 8.7% (11of 126) of cases, all in recipient twins. Significant differences in the rate of RVOTAs in the recipient twin were seen between TTTS cases with intermittent absent/reversed UA EDF and those with positive UA EDF (26.9% [7 of 26] versus 3.7% [3 of 82]; P = .002]. However, no significant differences were noted among the other study groups. Intermittent absent/reversed UA EDF was associated with a significantly increased risk for an RVOTA (adjusted odds ratio, 20.6 [95% confidence interval, 3.1-138]; P = .002) after adjusting for confounders. Intermittent changes in vascular impedance to UA flow may contribute to the pathogenesis of acquired right-sided cardiac lesions in the recipient twin affected with TTTS.

Renal artery Doppler studies in the assessment of monochorionic, diamniotic twin pregnancies with and without twin-twin transfusion syndrome

In monochorionic, diamniotic twin pregnancies complicated by twin-twin transfusion syndrome, imbalanced fetofetal blood shunting and discordant activation of the renin-angiotensin system result in a hypovolemic, oliguric donor twin and a hypervolemic, polyuric recipient twin. Renal artery Doppler assessments have been reported to predict oligohydramnios in singleton pregnancies; however, their value in assessing monochorionic, diamniotic twin gestations, including pregnancies complicated by twin-twin transfusion syndrome, remains unstudied. This investigation evaluated whether renal artery Doppler parameters are different between sets of monochorionic, diamniotic twins with and without twin-twin transfusion syndrome. We conducted a prospective study of women with monochorionic, diamniotic twin pregnancies complicated by twin-twin transfusion syndrome and women with gestational-age matched monochorionic, diamniotic twin control pregnancies without twin-twin transfusion syndrome. For each twin, renal artery Doppler assessment was performed from a coronal view of the fetus, and pulsatility index, resistive index, and peak systolic velocity were measured. In twin pairs complicated by twin-twin transfusion syndrome, renal artery Doppler pulsatility index, resistive index, and peak systolic velocity intertwin ratios were calculated by comparing paired recipient-to-donor values. Similar ratios were calculated for control twin pairs. We compared each measurement between donors and controls and between recipients and controls. Intertwin ratios were compared between twin-twin transfusion syndrome cases and monochorionic, diamniotic controls. Our primary outcome was a comparison of renal artery Doppler pulsatility index measurement between donor fetuses in twin-twin transfusion syndrome cases and matched control twins. Secondary outcomes included comparisons of other renal artery Doppler parameters between twin-twin transfusion syndrome donor twins and controls and between twin-twin transfusion syndrome recipients and controls and comparisons of the renal artery Doppler parameter ratios between twin-twin transfusion syndrome and non-twin-twin transfusion syndrome twin pair groups. Finally, we performed a subgroup analysis involving pregnancies with twin-twin transfusion syndrome that underwent fetoscopic laser therapy and resulted in twin survivors to evaluate if laser therapy influenced renal artery Doppler findings. We recruited 12 donors and 12 controls. Renal artery Doppler pulsatility index and resistive index did not differ between donors and controls. However, donor renal artery Doppler peak systolic velocity (median, 14.24 [11.51-15.36]) was significantly lower than that of controls (median, 24.79 [22.46-27.03]; P<.0004). When recipient twins were compared with controls, there was no difference in renal artery Doppler pulsatility index, renal artery Doppler resistive index, or renal artery Doppler peak systolic velocity. Renal artery Doppler peak systolic velocity ratios were significantly higher among cases with twin-twin transfusion syndrome (median, 1.70 [1.53-2.02]) than controls (median, 1.06 [1.03-1.15]; P=.002). Applying a renal artery Doppler peak systolic velocity ratio cutoff of >1.35 for the diagnosis of twin-twin transfusion syndrome correctly classified 11 of 12 cases with twin-twin transfusion syndrome and all 12 controls without twin-twin transfusion syndrome (92% sensitivity and 100% specificity). Among donors with twin-twin transfusion syndrome with double survivors after undergoing laser therapy (n=4), prelaser renal artery Doppler peak systolic velocity ratios (mean, 1.46; standard deviation, 0.37) were significantly higher than postlaser renal artery Doppler peak systolic velocity ratios (mean, 0.87; standard deviation=0.37; P=.02). Postlaser intertwin renal artery Doppler peak systolic velocity ratios did not differ from control twin pairs (P=.125). Renal artery Doppler peak systolic velocity ratios differ between monochorionic, diamniotic twins with twin-twin transfusion syndrome and those without twin-twin transfusion syndrome. This effect seems to be driven by altered donor twin renal artery Doppler peak systolic velocity. Laser therapy may normalize renal artery Doppler peak systolic velocity ratios and donor twin renal artery Doppler values to those observed in monochorionic, diamniotic twins without twin-twin transfusion syndrome. Further study is warranted to explore whether renal artery Doppler peak systolic velocity has utility as a tool for twin-twin transfusion syndrome prediction, diagnosis, or staging, and fetal response to laser therapy.

Prevalence, risk factors, and outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome: a large single-center case series

Postprocedural amniotic band disruption sequence is a condition that is associated with intrauterine interventions, and it is characterized by a constriction of the limbs or umbilical cord by fibrous strands, leading to edema, amputation, and/or fetal demise. To evaluate the prevalence of, risk factors for, and the outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome cases. All consecutive cases of twin-twin transfusion syndrome treated with fetoscopic laser coagulation of the vascular anastomoses at our center between January 2002 and March 2019 were included in the study. The occurrence of postprocedural amniotic band disruption sequence in these cases was recorded, and the potential risk factors were analyzed. Postprocedural amniotic band disruption sequence was detected, at birth, in 2.2% (15/672) of twin-twin transfusion syndrome cases treated with fetoscopic laser surgery, in both the recipients (10/15, 67%) and the donors (5/15, 33%). Postprocedural amniotic band disruption sequence primarily affected the lower extremities (11/15, 73%) and, less frequently, the upper extremities (2/15, 13%), both the upper and lower extremities (1/15, 7%), or the umbilical cord (1/15, 7%). Postprocedural amniotic band disruption sequence led to the amputation of toes in 5 of 15 cases (33%) and resulted in fetal demise because of constriction of the umbilical cord in 1 case (7%). The independent risk factors identified for postprocedural amniotic band disruption sequence were lower gestational age at laser surgery (odds ratio per week, 1.43; 95% confidence interval, 1.12-1.79; P=.003) and the presence of postprocedural chorioamniotic membrane separation on antenatal ultrasound examination (odds ratio, 41.66; 95% confidence interval, 5.44-319.25; P<.001). The prevalence of postprocedural amniotic band disruption sequence is low, but, when present, it may lead to severe consequences, with amputation of extremities or fetal demise occurring in more than one-third of the cases. Lower gestational age at the time of laser therapy and chorioamniotic membrane separation are independent risk factors for the postprocedural amniotic band disruption sequence.