Twin-twin Transfusion Syndrome Stage 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.

Disparities in fetal surgery access: Association with twin-twin transfusion syndrome stage at initial consultation

Among individuals with twin-twin transfusion syndrome (TTTS), we sought to determine if insurance type was associated with advanced TTTS disease at the time of surgical consultation. This was a retrospective cohort study of individuals with Quintero stage I-IV TTTS undergoing laser surgery at a single center, 2015-2021. Excluded individuals had out-of-state residency, higher order multiples, surrogate or monoamniotic gestations. Primary exposure was insurance type, defined as private/commercial insurance (Commercial), public fee for service (FFS) or traditional Medi-Cal (e.g., California Medicaid), and public Medi-Cal/Covered California Group Plans including self-pay (Group). Primary outcome was Quintero stage III/IV (high TTTS stage), as determined during initial surgical consultation. Secondary outcomes included gestational age and fetal growth restriction (FGR). We compared sociodemographic and obstetric variables at initial consultation across insurance type. Outcomes with p< 0.10 in bivariate analyses were tested using multiple logistic regression models; demographic data were tested for relevance as covariates. Of 362 individuals in this contemporary cohort, 243 met study criteria. The Table provides cohort demographics. Non-Hispanic White individuals were more likely to have Commercial insurance (44.2% vs. FFS 12.8% vs. Group 19.3%, p< 0.0001). In bivariate analyses, high TTTS stage and FGR were associated with insurance type. In adjusted logistic regression, Group insurance was associated with increased odds of presenting with high TTTS stages (OR 2.33, 95%CI 1.16-4.70) and FGR (OR = 2.02, 95%CI 1.06-3.86) (Figure). FFS insurance was not associated with any of these outcomes. Individuals with public Group plans were more likely than those with Commercial plans to present with higher stage TTTS and FGR at initial surgical evaluation, suggesting there may be gaps or delays in access to fetal surgical care for individuals with public insurance.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Correction of fetal umbilical vein flow imbalance following laser surgery for twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) is characterized by unequal hemodynamics between the twins. We aimed to assess preoperatively the difference in umbilical vein flow (UVF) between the recipient and donor monochorionic diamniotic twins and evaluate the change in UVF following laser surgery in both twins. This was a retrospective cohort study of differences in UVF that occurred following laser surgical treatment of TTTS. Sonographic assessment of the umbilical vein before and 24 h after fetoscopic laser surgery for TTTS was performed. Umbilical vein diameter and time-averaged maximum velocity were measured, and UVF per kg (UVF/kg) was converted into a Z-score by a calculator created using gestational age as an independent variable. Z-score values were converted into centiles, which were evaluated statistically. Median differences in UVF/kg centile values were adjusted for TTTS stage and presence of arterioarterial anastomoses. The study population consisted of 363 TTTS patients. The adjusted preoperative median difference in UVF/kg centile between the recipient vs donor twin was 17.9% (-17.1% to 57.6%), P < 0.0001. The adjusted median difference in UVF/kg centile between the postoperative vs preoperative period among recipients was 2.2% (-10.8% to 13.8%), P < 0.0001, while the adjusted median difference among donors was 27.3% (8.2%-34.6%), P < 0.0001. The preoperative difference in UVF between the recipient and donor twins confirms the pathophysiology of TTTS. Postoperatively, the substantial increase in UVF of the donor twin and the relatively small increase in UVF of the recipient twin confirm that ablation of the vascular communications resulted in rapid improvement in perfusion of the donor twin. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetoscopic Laser Ablation for the Selective Fetal Reduction in Twin-Twin Transfusion Syndrome Stage II-IV: The Experience of a New Fetal Medicine Center.

ObjectiveTo evaluate the surgery outcomes of fetoscopic laser ablation (FLA) for selective umbilical cord in treating twin-twin transfusion syndrome (TTTS) with special conditions and neonatal outcomes post-operation.MethodsA prospective study, 21 monochorionic diamniotic (MCDA) twins diagnosed with TTTS stage II–IV according to Quintero classification from 16 to 26 weeks of gestation, among that, 12 cases of TTTS stage II with selective intrauterine growth restriction (sIUGR), 6 cases of TTTS stage II with proximate cord insertions, 3 cases of TTTS stage IV underwent fetoscopic laser ablation for the selective fetal reduction at Hanoi Obstetrics and Gynecology Hospital from September 2019 to July 2021. Complications and surgical outcomes were noted. Prenatal care was carried out every 2 weeks post operation until birth. Newborn neurologic complications were assessed at birth, three months, and six months after birth using Denver II test and magnetic resonance imaging (MRI).ResultsThe mean gestational age at operation was 20.30 weeks. The average operation duration was 39.52 minutes. No complications of operation, such as bleeding or infection, were recorded. The mean gestational age at birth was 34.70 ± 4.33 weeks, with a mean duration of 12.97 ± 6.87 weeks between intervention and delivery. The survival rate of newborns after the operation was 90.48%. There were two stillbirths (9.52%) within seven days after the operation. No short-term neurological complications have been reported with follow-up of the newborn to 6 months after birth.ConclusionOur study showed that fetoscopic laser ablation of selected fetal reduction surgery for treatment of special conditions of TTTS had no complications of operation, high neonatal survival result (90.48%), no short-term neurological complications. This should be considered for TTTS in cases of indication.

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.

A donor twin discordant with Peters anomaly in a twin\u2013twin transfusion syndrome case: a case report

BackgroundPeters anomaly is a rare form of anterior segment ocular dysgenesis, the antenatal image of Peters anomaly had not been reported. We herein showcased a discordant finding of Peters anomaly in a monozygotic twin complicated with twin-twin transfusion syndrome (TTTS) and exhibited its antenatal sonographic images,Case presentationA 38-year-old gravida 2 para 1 pregnant woman visited our clinic at the gestational age of 18 weeks where TTTS stage III was diagnosed and the following laser therapy was done successfully. Ten days after the surgery, the follow-up ultrasound detected the opacity of both fetal eyeballs in the donor twin and thus congenital cataract was suspected initially. Then magnetic resonance imaging (MRI) examination was arranged at the gestational age of 23 weeks, and no central nervous system or other anomaly was found. At the 29 weeks of gestation, the opacity of both fetal eyeballs of the donor twin did not clear. The pregnancy resulted in cesarean section at the gestational age of 37 weeks indicated by malpresentation where two male live births were born. Examination under anesthesia was arranged for donor twin after delivery and Peters anomaly was diagnosed based on central corneal opacity with iridocorneal and corneolenticular adhesions.ConclusionsThe prenatal image of Peters anomaly may present as the opacity of the fetal eyeballs similar to congenital cataract. Some cases of the Peters anomaly had been reported with a genetic abnormality, but since our case presented discordant presentation in monozygotic twin pregnancy where both twins are supposed to share the same genetic make-up, therefore other factors that are epigenetic may be held accountable. Nevertheless, a genetic origin of the anomaly in our case cannot be excluded.

Percent Absent End-Diastolic Velocity and Risk of Donor Twin Demise in Twin-Twin Transfusion Syndrome [19A

INTRODUCTION: We examined the association of percent absent end-diastolic velocity (%AEDV) in the umbilical artery with intrauterine fetal demise (IUFD) of the donor twin after laser surgery in patients with twin-twin transfusion syndrome (TTTS) Quintero stages III/IV. %AEDV was calculated as 100x the proportion of total cardiac cycle spent in AEDV. METHODS: Retrospective study of TTTS stage III/IV patients between 2006 and 2016. Donors were classified as having persistent AEDV (yes/no). In Part 1, we used multiple logistic regression analysis to test whether AEDV was associated with donor IUFD. We stratified these analyses by estimated fetal weight (EFW) discordance of ≥20% or <20%. In Part 2, we used similar models to test only those with AEDV to determine whether %AEDV was associated with IUFD. This was an IRB approved study. RESULTS: Of 344 stage III/IV TTTS cases, 153 (44.5%) donors had preoperative AEDV. In Part 1, we did not confirm an independent association between AEDV and donor IUFD. In Part 2, patients with AEDV who were discordant (N=129), had the following characteristics associated with donor IUFD: %AEDV (OR 1.04, 95% CI 1.01-1.08), %EFW discordance (OR 1.07, 95% CI 1.02-1.13), and presence of arterioarterial anastomoses (OR 5.15, 95% CI 2.06-12.89). In the non-discordant group (N=24), no association was found between %AEDV and donor IUFD. CONCLUSION: The presence of preoperative persistent AEDV was not an independent risk factor for donor IUFD in stage III/IV TTTS patients undergoing laser surgery. However, among donors with preoperative AEDV and EFW discordance ≥20%, %AEDV was positively associated with donor IUFD.

North American Fetal Therapy Network: timing of and indications for delivery following laser ablation for twin-twin transfusion syndrome

Despite improvements in fetal survival for pregnancies affected by twin-twin transfusion syndrome since the introduction of laser photocoagulation, prematurity remains a major source of neonatal morbidity and mortality. To investigate the indications and factors influencing the timing of delivery following laser treatment, we collected delivery information regarding twin-twin transfusion syndrome cases in a large multicenter cohort. Eleven North American Fetal Therapy Network (NAFTNet) centers conducted a retrospective review of twin-twin transfusion syndrome patients who underwent laser photocoagulation. Clinical, demographic and ultrasound variables including twin-twin transfusion syndrome stage, and gestational age at treatment and delivery were recorded. Primary and secondary maternal and fetal indications for delivery were identified. Univariate analysis was used to select candidate variables with significant correlation with latency and GA at delivery. Multivariable Cox regression with competing risk analysis was utilized to determine the independent associations. A total of 847 pregnancies were analyzed. After laser, the average latency to delivery was 10.11 ± 4.8 weeks and the mean gestational age at delivery was 30.7 ± 4.5 weeks. Primary maternal indications for delivery comprised 79% of cases. The leading indications included spontaneous labor (46.8%), premature rupture of membranes (17.1%), and placental abruption (8.4%). Primary fetal indications accounted for 21% of cases and the most frequent indications included donor non-reassuring status (20.5%), abnormal donor Dopplers (15.1%), and donor growth restriction (14.5%). The most common secondary indications for delivery were premature rupture of membranes, spontaneous labor and donor growth restriction. Multivariate modeling found gestational age at diagnosis, stage, history of prior amnioreduction, cerclage, interwin membrane disruption, procedure complications and chorioamniotic membrane separation as predictors for both gestational age at delivery and latency. Premature delivery after laser therapy for twin-twin transfusion syndrome is primarily due to spontaneous labor, preterm premature rupture of membranes and non-reassuring status of the donor fetus. Placental abruption was found to be a frequent complication resulting in early delivery. Future research should be directed toward the goal of prolonging gestation after laser photocoagulation to further reduce morbidity and mortality associated with twin-twin transfusion syndrome.

Cardiac pathophysiology in twin-twin transfusion syndrome: new insights into its evolution.

In twin-twin transfusion syndrome (TTTS), unbalanced transfer of vasoactive mediators and fluid from the donor to the recipient cotwin alters their cardiovascular function. The aims of this study were to describe the impact of TTTS on fetal cardiac function in a large cohort of monochorionic-diamniotic (MCDA) pregnancies, and determine the early hemodynamic response to selective fetoscopic laser photocoagulation (SFLP). Echocardiography was performed in 145 MCDA pregnancies, including 26 uncomplicated MCDA, 61 TTTS Stages I+II and 58 TTTS Stages III+IV pregnancies, prior to SFLP for TTTS. Echocardiographic data after SFLP were available in a subset of 41/119 (34%) TTTS cases at a mean of 1.7 ± 1.9 days. Mitral (MAPSE) and tricuspid (TAPSE) annular systolic excursion, myocardial performance index (MPI), tissue Doppler velocities (E', A', S') and filling pressures (E/E') were measured and transformed into Z-scores. Ventricular pressure was estimated from peak atrioventricular regurgitation velocity. Left ventricular hemodynamics of the recipient twin were affected in early TTTS. In all stages of TTTS, left MPI and E/E' of the recipient twin were elevated in comparison to those of the donor (all P < 0.05), with reduced recipient left S' in TTTS Stages III+IV (P < 0.001). Ventricular pressure was elevated for gestational age (median, 42 mmHg (range, 20-65 mmHg)) in 11 of 14 recipients in which this parameter was measured. Between-group difference in right ventricular E/E' was significant only in TTTS Stages III+IV recipients compared with TTTS Stages I+II (P = 0.007) and uncomplicated MCDA (P = 0.041). Recipient left and right MPI decreased while S', MAPSE and TAPSE increased after SFLP; in donors, left E/E' and cardiac output increased. Cardiac function of the recipient twin in TTTS is abnormal, even in the early stages of the disease. Left ventricular filling pressures are elevated and systolic function is decreased before abnormalities in the right heart become apparent. SFLP produces rapid hemodynamic improvement. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

528: North American Fetal Therapy Network: Indications for delivery following laser ablation for twin-twin transfusion syndrome

Despite improvements in fetal survival for pregnancies affected by twin-twin transfusion syndrome (TTTS) since the introduction of laser photocoagulation, prematurity remains a major source of morbidity and mortality. To investigate the role that iatrogenic and procedure-related factors contribute to prematurity, we collected information regarding timing and indication for delivery following laser treatment in a multicenter cohort. Eleven centers from the North American Fetal Therapy Network (NAFTNet) conducted a retrospective review of consecutive cases of TTTS undergoing laser treatment recording clinical and ultrasound variables including TTTS Stage and gestational age (GA) at treatment and delivery. The route as well as the primary and secondary maternal or fetal indications for delivery were noted. Spearman correlations were utilized to determine variables with significant correlation with latency and GA at delivery. Multivariable modeling was utilized to determine the strongest associations. A total of 749 pregnancies were analyzed. Treatment details and outcomes are listed in Table 1. After laser, average latency is 10.2 ± 4.8 weeks and mean GA at delivery 30.7 ± 4.5 weeks. Primary maternal indications for delivery comprised 75% of cases and included spontaneous labor (46.2%), premature rupture of membranes (PROM) (17.6%), and abruption (8.1%). Primary fetal indications included donor non-reassuring fetal surveillance (20.8%), donor growth restriction (16.1%) and abnormal Doppler (16.1%). The most common secondary indications for delivery are PROM, spontaneous labor and donor growth restriction. Table 2 lists the variables with significant correlations to GA at delivery or latency under univariate analysis. After multivariable modeling, cerclage and fetoscopic complications are associated with shorter latency and earlier GA at delivery whereas a history of preterm birth is associated with shorter latency. In our cohort, premature delivery after laser therapy was primarily due to spontaneous labor, PROM or concern regarding the donor. Both modifiable and non-modifiable factors correlated with earlier delivery and shorter latency. Future research should be directed toward the goal of prolonging pregnancy to further reduce morbidity and mortality associated with TTTS.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Risk factors for fetomaternal bleeding after laser therapy for twin-twin transfusion syndrome.

To quantify and assess potential risk factors for transplacental passage of fetal red blood cells (RBCs) into the maternal circulation (fetomaternal bleeding, FMB) after laser surgery for twin-twin transfusion syndrome (TTTS). A retrospective study of Rhesus-D negative patients that underwent laser surgery for TTTS. Patients with and without postoperative detectable fetal RBCs on Kleihauer-Betke (KB) testing were compared to determine risk factors for FMB. Patients were further sub-classified into those with a FMB<20% and ≥20% of estimated fetoplacental blood volume. Of 60 studied patients, 26/60 (43%) had a positive postoperative KB test. The median fetal:adult RBC ratio was 0.00125, estimated to be a FMB volume of 6.25mL. There were 17/26 (65%) of patients with FMB<20% and 9/26 (35%) patients with ≥20% of the fetoplacental blood volume. Stage III-Recipient and III-Recipient/Donor patients were more likely to have a positive KB test (14/21 [66.7%] vs 12/39 [30.8%], OR=4.50 [1.27-16.54], P=0.0162). No other risk factors for FMB were apparent. Fetomaternal bleed appears to be a common finding after laser surgery for TTTS. TTTS Stage, particularly stage III-Recipient and III-Recipient/Donor, appears to be a risk factor for FMB.

Recipient umbilical artery elongation (redundancy) in twin-twin transfusion syndrome

Chronic hypertension in adults causes arterial lengthening in major arteries, but the effects of early fetal hypertension on the twin-twin transfusion syndrome recipient's vascular architecture remains unknown. We hypothesize that arterial cord redundancy is related to recipient hypertension and subsequent heart failure. Our objectives were to: (1) establish a 3-dimensional color Doppler ultrasound method of measuring umbilical arterial length relative to its corresponding venous segment in the umbilical cord using artery vein angle; (2) compare recipient artery vein angle to gestational age-matched controls; and (3) test the association of artery vein angle with recipient heart failure. We compared 3 groups prospectively: twin-twin transfusion syndrome pregnancies undergoing fetoscopic laser surgery (preoperatively) and 2 groups of gestational age-matched controls: uncomplicated monochorionic-diamniotic twin pregnancies and healthy singletons. Using a 3-dimensional color-Doppler volume image of 5 cm of cord near the placental insertion, we traced the umbilical artery and vein producing umbilical artery:vein length, (artery vein index) and measured the artery vein angle between umbilical artery and vein. Correlation of artery vein angle to twin-twin transfusion syndrome stage, maximum vertical pocket, umbilical arterial indices, ductus venosus Doppler, and brain natriuretic peptide were performed. We used pulsed-wave and tissue Doppler to measure tissue Doppler velocities and indexed cardiac output and correlated these with artery vein angle. Comparative statistics, including multivariable linear regression, examined the relationship between umbilical arterial Doppler indices and artery vein angle. Artery vein angle and artery vein index correlated significantly (R2, 0.86; P < .0001), hence, artery vein angle was used for analysis. Mean artery vein angle was 33.1 ± 31.5 degrees in recipients (n= 44), 9.5 ± 6 degrees in monochorionic-diamniotic (n= 11; 22 fetuses), and 8.9 ± 8.3 degrees in singleton controls (n= 16) (P < .001). An artery vein angle ≥26 degrees (>95th percentile for controls) was measured in 52% recipients. Artery vein angle was higher in twin-twin transfusion syndrome stage 3R vs 1 (P= .001). Artery vein angle increased with increasing umbilical arterial pulsatility index (P < .001), and decreased with increasing resistance index (P= .02) after adjusting for gestational age. Interrater agreements to categorize abnormal artery vein angle values was 95% (P < .001). Abnormal ductus venosus Doppler and elevated recipient amniotic fluid N-terminal pro-brain natriuretic peptide/protein levels correlated significantly with artery vein angle. Abnormal artery vein angles were associated with decreased indexed cardiac output, lower tissue Doppler velocities, higher right-sided Tei indices, and severe tricuspid regurgitation. Umbilical arterial lengthening occurs in 52% of recipients and is associated with abnormal Doppler flows, low systolic tissue Doppler velocities, reduced cardiac output, and elevated markers of cardiac failure. This may reflect chronicity and severity of hypertension in the recipient fetus. Further research is needed to explore the mechanisms of elongation and long-term implications.

Changes in ductus venosus flow profile in twin-twin transfusion syndrome: role in risk stratification.

To evaluate changes in ductus venosus (DV) waveforms and the timing of these changes in twin-twin transfusion syndrome (TTTS), to relate these to disease severity and to assess the clinical applicability of the suggested measurements in the prediction of TTTS. DV time intervals and velocity-time integrals (VTI) normalized to cardiac cycle and total VTI, respectively, as well as velocity ratios were analyzed in 149 monochorionic diamniotic (MCDA) twin pairs. Pregnancies were assigned to the following groups: uncomplicated MCDA (n = 29); TTTS Stages I+II (n = 50); TTTS Stages III+IV (n = 49); and pre-TTTS (n = 21), of which 14 remained stable and seven progressed to TTTS. Intertwin differences were calculated as larger/recipient minus smaller/donor and related to disease severity. Receiver-operating characteristics curve analysis was used to distinguish TTTS vs uncomplicated MCDA and pre-TTTS progressing to TTTS vs non-progressing pre-TTTS. Intra- and interobserver reliability of measurement of DV parameters were evaluated using intraclass correlation coefficients (ICCs). No intertwin differences in DV parameters were found in uncomplicated MCDA pregnancies. Diastolic VTIs and filling times were significantly shorter in recipient twins in TTTS cases and in larger pre-TTTS twins in comparison with their cotwins. Time intervals, VTIs and velocity ratios correlated significantly with Quintero stages. An intertwin difference in early filling time (eT) normalized to cardiac cycle, eT (%) ≤ -3.6%, could differentiate TTTS from uncomplicated MCDA pregnancies (82.8% sensitivity; 79.8% specificity) and eT (%) ≤ -2.8% predicted progression to TTTS (73.1% sensitivity; 67.4% specificity). DV flow profiles and timing of waveform events are already altered in pre-TTTS and early-stage disease, reflecting abnormal ventricular filling and circulatory imbalance. Intertwin comparison of filling times and VTI may allow prediction of evolving TTTS in MCDA pregnancies. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Aortic distensibility as a surrogate for intertwin pulse pressure differences in monochorionic pregnancies with andwithout twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates 10-15% of monochorionic diamniotic (MCDA) twin pregnancies. The donor response to hypovolemia allows the transfer of vasoactive mediators to the recipient, causing increased recipient afterload and hypertension. Our objective was to apply a novel speckle-tracking technique to measure the aortic fractional area change (AFAC) during the cardiac cycle in MCDA twins with and without TTTS, and identify intertwin differences in AFAC and parameters of cardiac function. High-frame rate four-chamber views of the fetal heart, including the mid-thoracic aorta, were collected prospectively in MCDA twin pairs referred to our center between June 2014 and April 2015. Using speckle-tracking software, the endovascular border of the aorta was traced manually during systole, with guidance on cardiac cycle timing by anatomical M-mode. AFAC, defined as the difference between maximum and minimum area divided by minimum area, expressed as a percentage, was calculated offline and averaged over three cardiac cycles. Tissue Doppler and displacement were used to measure long-axis cardiac function. Intra- and interclass correlation coefficients were used to test observer variability. Fifty-one MCDA twin pregnancies were included, comprising uncomplicated MCDA (n = 14), TTTS Stages 1/2 (n = 21) and TTTS Stages 3/4 (n = 16). Median gestational age was 20.4 (range, 16.2-27.5) weeks. Mean ± SD heart rate was 142.6 ± 7.2 bpm with no significant intertwin pair differences. AFAC was significantly higher in recipients than in donors of TTTS pairs (Stages 1/2: 72.3 ± 29.9% vs 43.7 ± 19.3%, P < 0.001; Stages 3/4: 75.2 ± 29.2% vs 42.5 ± 18.4%, P = 0.002), consistent with higher recipient pulse pressure. No intertwin differences in AFAC were seen in uncomplicated MCDA pairs. Inter- and intraclass correlation coefficients for AFAC were 0.894 and 0.888. AFAC correlated significantly with combined cardiac output (r = 0.252, P = 0.011) and left and right E/E' ratio (left: r = 0.302, P = 0.004; right: r = 0.247, P = 0.030). AFAC is a quantifiable and reproducible method to assess aortic distensibility and is a promising tool to monitor the response to prelaser therapeutic interventions in pregnancies with TTTS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

2095290 Sonography Interval and Diagnosis of Twin-Twin Transfusion Syndrome

To evaluate the relationship between sonographic surveillance for twin-twin transfusion syndrome (TTTS) and gestational age and stage at diagnosis. We reviewed monochorionic diamniotic pregnancies with TTTS followed with serial sonography at a single institution from 1997 to 2013. All sonogram images were reviewed by an investigator to confirm Quintero stage. Gestational age and stage were compared in those diagnosed at initial sonogram or at a subsequent sonogram either within or >14 days from a prior exam. TTTS was diagnosed in 48 pregnancies, 50% at the 1st, 19% at the 2nd, and 31% at or after the 3rd sonogram. Overall, 50% were stage I, 10% stage II, 29% stage III, and 10% stages IV or V at diagnosis. Those diagnosed at initial sonogram developed disease earlier than those diagnosed during a subsequent exam, 21.4±3.6 weeks vs 25.1±4.3 weeks, P=0.001, but there was no difference in TTTS stage at diagnosis, P=0.2. Among those diagnosed during a follow-up sonogram, 29% had isolated oligohydramnios and 17% isolated hydramnios at the sonogram preceding diagnosis. Isolated fluid abnormalities were more common if the prior exam was within 14 days than if >14 days, 70% vs. 21%, P=0.01. Stage III was more likely to be diagnosed ≤14 days from a prior sonogram than with longer scanning interval, P=0.04 (Table), otherwise there was no difference in TTTS stage at diagnosis in relation to sonogram interval. TTTS stage did not differ whether the diagnosis was made at an initial or subsequent sonogram. Sonography interval >14 days was not associated with more advanced stage at diagnosis. Isolated oligohydramnios or hydramnios on prior ultrasound was associated with shorter interval to diagnosis, reflecting increased surveillance for fluid abnormalities.Tabled 1Sonography Interval and Diagnosis of TTTSDiagnosed at Initial SonogramSonogram Interval ≤ 14 daysSonogram Interval > 14 daysStagen (%)Gestational Age, weeksn (%)Gestational Age, weeksn (%)Gestational Age, weeksI11 (46)21.23 (30)24.810 (71)27.3II4 (17)21.11 (10)26.10-III6 (25)20.56 (60)22.32 (14)23.0IV1 (4)25.50-2 (14)24.7V2 (8)23.20-0- Open table in a new tab

Altered amniotic fluid leptin levels in twin–twin transfusion syndrome with concurrent placental insufficiency

Objective: To measure amniotic fluid leptin levels in fetuses with twin–twin transfusion syndrome (TTTS) with and without placental insufficiency (PI) and determine its usefulness as a biomarker of PI.Study design: A retrospective case control study of TTTS stage III patients from 2009 to 2011 was conducted. Cases were pregnancies with PI (TTTS-PI, n = 18) matched by stage, gestational age, and degree of cardiomyopathy to controls without PI (TTTS, n = 26). PI was strictly defined using biometric parameters. Amniotic fluid from recipient twins (RT) was taken during second trimester fetoscopic laser therapy. Leptin concentrations were determined and compared to growth parameters and birth weight.Results: RT-adjusted leptin was 66% higher in TTTS-PI (p = 0.016) compared to TTTS controls. Cases had significantly higher growth discordance (p = 0.004) and lower RT birth weight (p = 0.041) compared to controls. Significantly higher adjusted leptin levels were observed at birth in the TTTS-PI group when comparing those with SGA donor twins to those of normal weight (p = 0.016).Conclusion: These data suggest a role for leptin in pregnancies complicated by TTTS with placental insufficiency. However, further studies are needed to define its mechanism and potential role as a biomarker in amniotic fluid for placental pathophysiology.

Prenatal management and outcomes in mirror syndrome associated with twin-twin transfusion syndrome.

The aim of this article is to investigate the prevalence, clinical presentation, prenatal management, and prognosis of mirror syndrome associated with twin-twin transfusion syndrome (TTTS) treated by amnioreduction or selective fetocide. A retrospective study of twin pregnancies with TTTS was conducted. The prevalence of mirror syndrome, defined as severe maternal edema related to fetal hydrops and placental edema, was calculated for TTTS, and data on clinical characteristics, treatment, and outcomes of the patients were reviewed. We observed mirror syndrome in 4.85% (5/103) of pregnancies with TTTS and 26.32% (5/19) of pregnancies with TTTS Stage IV. Most cases (4/5) of mirror syndrome associated with TTTS were diagnosed before 24 weeks of gestation. The patients manifested edema, anemia, hemodilution, and hypoproteinemia (5/5); proteinuria (4/5); complicated postpartum hemorrhage (4/5); and pulmonary edema and congestive heart failure (2/5). Maternal hemoglobin, hematocrit, and plasma protein dropped after amnioreduction. The perinatal survival rate at 28 days was 28.57% (2/7), and only one infant born after selective feticide survived beyond 18 months. TTTS carries a high risk of mirror syndrome, a disease with significant materno-fetal mortality and morbidity. Amnioreduction alone or with selective feticide in mirror syndrome may transiently aggravate anemia and hemodilution and lead to severe maternal complications. © 2014 John Wiley & Sons, Ltd.

Twin–twin transfusion syndrome: a frequently missed diagnosis with important consequences

To evaluate the incidence and consequences of 'misdiagnosed' cases of twin-twin transfusion syndrome (TTTS). Chorionicity and referral diagnoses were reviewed in pregnant women with monochorionic twin pregnancies complicated by TTTS treated with fetoscopic laser ablation. 'Misdiagnosed' cases, defined as failure to correctly identify chorionicity and/or to diagnose TTTS prior to referral, were compared with cases in whom chorionicity and TTTS were diagnosed correctly. TTTS stage, gestational age at referral, overall survival, fetal and perinatal mortality, gestational age at delivery, operating time and maternal complications were compared. Failure to identify monochorionicity and/or TTTS was observed in 33% (107/323) of referrals to our center. Compared with cases in whom chorionicity and TTTS were correctly diagnosed, misdiagnosed patients were referred at a more advanced stage of disease (Stage IV TTTS: 16.8% vs 7.9%, P = 0.014) and later in pregnancy (gestational age at laser: 20.9 weeks vs 20.1 weeks, P = 0.018). They also delivered more prematurely (30.3 weeks' gestation vs 31.5 weeks' gestation, P = 0.04) and fetal and neonatal mortality were higher (neonatal death within 7 days: 19.6% vs 6.0%, P < 0.001). When the diagnosis was incorrect, major maternal complications and intensive care unit admissions were increased. Poor recognition of chorionicity in the first trimester of pregnancy might lead to inadequate ultrasound follow up (failure to assess every 2 weeks) and patient education. Early accurate recognition of both chorionicity and TTTS, with timely referral to a fetal therapy center, are key to ensuring optimal maternal and fetal outcomes.

Fetoscopic Laser Therapy for Twin-Twin Transfusion Syndrome

Ever since the first randomized, controlled trial revealed that fetoscopic laser photocoagulation achieved better outcomes than serial amnio-drainage for all stages of twin-twin transfusion syndrome (TTTS) before 26 weeks, many centers have launched their fetoscopic laser therapy program for TTTS. Initially the nonselective method of laser therapy was applied, using the dividing membrane as a landmark to coagulate the placenta vessels, but currently selective methods (selective laser photocoagulation of communicating vessels (SLPCV), sequential SLPCV, and Solomon technique) have evolved to become the mainstream laser treatment modalities. Nevertheless, the nonselective method still has a role in difficult operations. Over the years, with regard to the prognoses of TTTS treated by laser, the attention has gradually shifted from survival rate to the neurological outcomes. The incidence of severe neurodevelopmetal delay remains considerably high in survivors of TTTS treated by FLP, which some reports cited ranging from 6 % to 18 %; learning curve effect exists, affecting both the survival rate and neurological outcomes of TTTS treated by laser. Because more, yet smaller and less-experienced, centers are being set up worldwide, the purpose of this manuscript is to review the basic knowledge and update information about the laser therapy for TTTS.

Global gene expression analysis of amniotic fluid cell‐free RNA from recipient twins with twin–twin transfusion syndrome

The objective of this study was to understand the biological pathways involved in twin-twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA. A prospective whole transcriptome microarray study analyzing cell-free RNA in AF from TTTS recipient twins and singleton controls was carried out. Significantly differentially regulated genes in TTTS cases (N = 8) versus matched controls (N = 8) were identified and pathways analyses performed. Significant gene expression differences between stage II TTTS recipients (N = 5) and stage III TTTS recipients with abnormal Doppler measurements (N = 5) were also analyzed. Analysis of paired data from TTTS cases and controls revealed differential expression of 801 genes, which were significantly enriched for neurological disease and cardiovascular system pathways. We also identified cardiovascular genes and pathways associated with the presence of critically abnormal Doppler measurements in stage III TTTS recipients. This study provides the first transcriptome-wide data on the impact of TTTS on fetal development. Our results show that gene expression involving neurological and cardiovascular pathways are altered in recipient fetuses prior to surgical treatment. This has relevance for the origins of long-term complications seen in survivors and for the development of future fetal biomarkers.