Twin twin transfusion syndrome with and without selective fetal growth restriction: Predictors of donor demise.

OBJECTIVE: Evaluate survival in twin twin transfusion syndrome (TTTS) with and without selective fetal growth restriction (sFGR) after fetoscopic laser surgery (FLS). METHODS: Retrospective study of monochorionic diamniotic twins undergoing FLS. The cohort was classified as TTTS and TTTS with sFGR. Baseline, intra-operative and postoperative variables were analyzed. Mann-Whitney U, Pearson chi-square, Fisher's exact, t-test and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Four hundred and ninety-two pregnancies were included, 304 (61.78%) TTTS and 188 (38.22%) TTTS with sFGR. No difference in donor outcomes. TTTS group had higher donor estimated fetal weight (EFW%) percentile (19.7 ± 18.8 vs. 2.2 ± 2.1, p < 0.001). Significant predictors for demise at 30 days were 37% intertwin weight discordance (IWD) with donor EFW% < first (area under ROC curve [AUC] = 0.85, p = 0.001) or IWD >25% and intertwin umbilical artery pulsatility index discordance (DUAPI) ≥0.4 (AUC = 0.71, p = 0.001). CONCLUSION: Combination of IWD of 37% and donor EFW%

Intertwin differences in umbilical artery pulsatility index are associated with infant survival in twin-to-twin transfusion syndrome.

OBJECTIVES: To evaluate the association of intertwin differences in umbilical artery pulsatility index (DUAPI) and infant survival in twin-to-twin transfusion syndrome (TTTS). METHODS: Absolute DUAPI was calculated prior to laser surgery. Receiver-operating characteristics (ROC) curve analysis provided an intertwin DUAPI cutoff of 0.4 for the prediction of double twin survival to 30 days of life. Infant survival was compared between women with an intertwin DUAPI <0.4 and ≥0.4 in the whole cohort, in TTTS cases with Quintero stages I/II and in those with Quintero stages III/IV. Regression analyses were performed to evaluate the association of intertwin DUAPI <0.4 and infant survival adjusted for confounders. RESULTS: In total, 349 TTTS cases were included. Double twin survival to 30 days was observed in 67% (234/349) of cases. Significant differences in double twin survival was seen between intertwin DUAPI groups in the whole cohort (76.8 vs. 52.2%; p<0.001), in women with TTTS Quintero stage I or II (77.8 vs. 58.5%; p=0.015) as well as in women with TTTS Quintero stage III or IV (75 vs. 49.5%; p=0.001). Intertwin DUAPI <0.4 conferred a threefold increased chance for double twin survival. CONCLUSIONS: Small intertwin DUAPI is associated with increased double infant survival in early and advanced TTTS stages.

Pregnancy outcomes and placental characteristics of selective intrauterine growth restriction with or without twin anemia polythemia sequence.

INTRODUCTION: To investigate differences in the pregnancy outcomes and placental characteristics of selective intrauterine growth restriction (sIUGR) with or without twin anemia polythemia sequence (TAPS). METHODS: sIUGR patients were assigned into two groups based on the occurrence of TAPS. The pregnancy outcomes and placental characteristics were compared. A diameter of ≥2 mm was defined as thick anastomosis. RESULTS: The prevalence of artery-to-artery (AA) (45.5% vs 88.6%, P = 0.002) and thick AA (0% vs 53.5%) in TAPS group were lower than non-TAPS group. The overall diameter of AA (0.5 (0.4-1.3) vs 2.5 (0.3-7.1) mm, P = 0.001) in TAPS group was smaller than non-TAPS group. The prevalence of thick artery-to-vein (AV) (0% vs 36.0%) in TAPS group was lower than non-TAPS group. Also, the overall diameter of AV (0.9 (0.6-2.1) vs 4.8 (0.3-17.8) mm, P < 0.001) in TAPS group was smaller than non-TAPS group. The total quantity (2 (1-6) vs 6 (1-16), P = 0.001), and the overall diameter of anastomoses (1.1 (0.6-4.7) vs 7.5 (0.5-22.4) mm, P < 0.001) were smaller in TAPS group than non-TAPS group. The placental territory discordance ratio of TAPS group was smaller than non-TAPS group (0.39 (0.13-0.56) vs 0.56 (0.01-0.88), P = 0.008). The umbilical cord insertion distance ratio in TAPS group was higher than non-TAPS group (0.81 ± 0.12 vs 0.57 ± 0.20, P < 0.001). DISCUSSION: The placental anastomoses of sIUGR with TAPS were small. sIUGR with TAPS had smaller differences in placental share and larger distances between umbilical cord insertions.

Perioperative fetal hemodynamic changes in twin-twin transfusion syndrome and neurodevelopmental outcome at two years of age.

OBJECTIVE: To investigate whether perioperative fetal hemodynamic changes in twin-to-twin transfusion syndrome (TTTS) are associated with neurodevelopmental impairment (NDI) at two years. METHODS: Doppler parameters of three sonograms (day before, first day after and 1 week after laser surgery for TTTS) were assessed for correlation with neurodevelopmental outcome at two years (2008-2016). NDI was defined as: cerebral palsy, deafness, blindness, and/or a Bayley-III cognitive/motor developmental test-score > 2SD below the mean. RESULTS: Long-term outcome was assessed in 492 TTTS survivors. NDI was present in 5% (24/492). After adjustment for severe cerebral injury (present in 4%), associated with NDI were: middle cerebral artery peak systolic velocity (MCA-PSV) >1.5 multiples of the median (MoM) 1 day after surgery (odds ratio [OR] 4.96; 95% confidence interval [CI]: 1.17-21.05, P = .03), a change from normal umbilical artery pulsatility index (UA-PI) presurgery to UA-PI >p95 postsurgery (OR 4.19; 95% CI: 1.04-16.87, P = .04), a change from normal to MCA-PSV >1.5MoM (OR 4.75; 95% CI: 1.43-15.77, P = .01). CONCLUSION: Perioperative fetal hemodynamic changes in TTTS pregnancies treated with laser are associated with poor neurodevelopmental outcome. Prospective research on the cerebrovascular response to altered hemodynamic conditions is necessary to further understand the cerebral autoregulatory capacity of the fetus in relation to neurodevelopmental outcome.

Percent Absent End-Diastolic Velocity in the Umbilical Artery and Donor Twin Demise after Laser Surgery for Twin-Twin Transfusion Syndrome.

INTRODUCTION: To examine the association of preoperative absent end-diastolic velocity (AEDV) and percent AEDV (%AEDV) in the umbilical artery (UA) with donor twin intrauterine fetal demise (IUFD) after laser surgery for twin-twin transfusion syndrome (TTTS). METHODS: We performed a retrospective study of stage III/IV TTTS patients who underwent laser surgery from 2006 to 2016. Donors were classified as having preoperative persistent AEDV (yes/no). %AEDV was calculated for those with AEDV as 100× the proportion of the total cardiac cycle in AEDV. Using multiple logistic regression, we tested for an association between the outcome donor IUFD and AEDV risk factors (part 1) and %AEDV (part 2). We stratified these analyses by estimated fetal weight (EFW) discordance ≥20 versus <20%. RESULTS: Of 344 cases, 153 (44.5%) donors had AEDV. Part 1 did not confirm an independent association between AEDV and donor IUFD. In the part 2 analysis of the 153 patients with AEDV, %AEDV was a positive risk factor for donor IUFD only in those with discordance (n = 129) (OR 1.04, 95% CI 1.01-1.08, p = 0.0278) when adjusting for %EFW discordance, presence of arterioarterial anastomoses, and multiparity. DISCUSSION: Among stage III/IV TTTS patients with AEDV, %AEDV was a risk factor for donor IUFD only in the presence of EFW discordance.

Asymmetrical Hemodynamic Influence of Twin-Twin Transfusion Syndrome on Fetal E/e' by the Dual Gate Doppler Method in Recipient Twins.

OBJECTIVES: To assess the hemodynamic influence of twin-twin transfusion syndrome (TTTS) on diastolic function, using left ventricle (LV) and right ventricle (RV) E/e' measured in the same cardiac cycle using the dual-gate Doppler (DD) method. METHODS: This study included 56 monochorionic twin pregnancies that underwent fetoscopic laser surgery (FLS) for TTTS in 2015-2018. E/e' by the DD method was measured 24 h before and 4-7 days after FLS. RESULTS: Recipients showed higher LV-E/e' Z score in stage I-, II-, and III-recipients (IIIr) and higher RV-E/e' Z score in stage III-donors and IIIr than donors (p < 0.05). After FLS, LV-E/e' Z score of recipients significantly decreased due to LV-E velocity Z score decrease (p < 0.05). RV-E/e' Z score after FLS significantly decreased due to RV-e' velocity Z score increase in recipients (p < 0.05). CONCLUSIONS: E/e' by the DD method helped assess cardiac changes of recipients. LV-E/e' could assess early hemodynamic changes by TTTS, and RV-E/e' can assess later influence on cardiac diastolic function. Furthermore, in recipient twins, the decrease in LV-E/e' after FLS might reflect the improvement of volume overload and the decrease in RV-E/e' might reflect the improvement of diastolic relaxation function in the RV.

Fetal ventricular strain in uncomplicated and selective growth-restricted monochorionic diamniotic twin pregnancies and cardiovascular response in pre-twin-twin transfusion syndrome.

OBJECTIVES: Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin-twin transfusion syndrome (TTTS). Secondary aims were to create gestational-age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS. METHODS: In the period 2015-2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four-chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16-26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed-effects multilevel regression. Inter-rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within-fetus variation was assessed in 16 such fetuses, in which multiple four-chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as 'pre-TTTS' when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the 'non-TTTS' group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non-TTTS and pre-TTTS cases, matched for gestational age. RESULTS: Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre-TTTS and 113 non-TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28-220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2-26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non-TTTS and 13/14 pre-TTTS MCDA twin pregnancies < 20 completed gestational weeks (RV, P = 0.338; LV, P = 0.932). DVeT% discordance > 3.6% was found in eight of 13 pre-TTTS pregnancies. In non-TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P < 0.001) and LV (P = 0.025) strain showed a negative association with gestational age. Among non-TTTS MCDA twin pregnancies, LV strain was, on average, higher by 1.83 in sIUGR compared with normally grown fetuses (P = 0.023), with no statistically significant difference in RV strain (P = 0.271). CONCLUSIONS: Although ventricular strain has been reported previously as a possible predictor of developing TTTS, in this blinded, prospective study, we found no significant intergroup differences in ventricular strain in pre-TTTS compared with age-matched non-TTTS MCDA twin pregnancies. We recommend using DVeT% discordance as a more practical screening tool in MCDA twin pregnancies. This study also provides new information on the changes with gestational age, and the biological and technical variation, of global longitudinal ventricular strain in uncomplicated MCDA twin pregnancies and those with isolated sIUGR. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association between impedance to blood flow in umbilical arteries and infant survival in twin-to-twin transfusion syndrome.

OBJECTIVE: To evaluate infant survival according to the Doppler pattern of impedance to blood flow in the umbilical arteries (UAs) prior to laser surgery, in pregnancies with twin-to-twin transfusion syndrome (TTTS). METHODS: This was a retrospective study of women with a monochorionic diamniotic twin pregnancy who underwent laser surgery for TTTS between January 2012 and May 2018 at a single institution. Absolute intertwin difference in UA pulsatility index (DUAPI) was measured within 48 h prior to laser surgery. Twins with intermittent or persistent absent/reversed end-diastolic flow (EDF) in the UA (UA-EDF) were analyzed separately. Survival of both or at least one infant at birth and at 30 days postpartum was compared between pregnancies with an intertwin DUAPI of ≥ 0.4 and those with an intertwin DUAPI of < 0.4, as well as between fetuses with intermittent and those with persistent absent/reversed UA-EDF. Parametric and non-parametric tests were used for analysis. Regression analysis was performed to determine if intertwin DUAPI and intermittent or persistent absent/reversed UA-EDF were associated independently with infant survival, while controlling for gestational age at delivery, Quintero stage and other important confounding variables. RESULTS: Of 231 TTTS pregnancies that underwent laser surgery during the study period, UA Doppler information could be retrieved for 206 and delivery information was available for 184, which comprised the study population. Rates of double-twin survival at birth were significantly higher in pregnancies with an intertwin DUAPI of < 0.4 than in those with an intertwin DUAPI of ≥ 0.4 (83.9% (78/93) vs 50.0% (12/24); P < 0.001). Double-infant survival at birth was higher in pregnancies with intermittent compared to those with persistent absent/reversed UA-EDF (73.0% (27/37) vs 36.7% (11/30); P = 0.003). Regression analysis demonstrated that an intertwin DUAPI of < 0.4 was associated with increased survival of both twins at delivery (P < 0.001) and at 30 days postpartum (P = 0.002), as well as increased survival of at least one twin at delivery (P = 0.009). Similarly, intermittent absent/reversed UA-EDF was associated with increased survival of both twins at delivery (P = 0.007) and at 30 days after birth (P = 0.015). CONCLUSIONS: Evaluation of intertwin differences in UA impedance to blood flow as well as identification of intermittent or persistent absent or reversed UA-EDF prior to laser surgery could help in the prediction of double-infant survival at birth and to 30 days in twin pregnancies with TTTS. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Neonatal Outcomes and Maternal Characteristics in Monochorionic Diamniotic Twin Pregnancies: Uncomplicated versus Twin-to-Twin Transfusion Syndrome Survivors after Fetoscopic Laser Surgery.

Preterm birth remains a major complication of fetal laser surgery (FLS) due to twin-to-twin transfusion syndrome (TTTS). OBJECTIVES: We tested the hypothesis that neonatal outcomes in fetuses born at >24 weeks are worse in TTTS survivors compared to uncomplicated monochorionic diamniotic (MCDA) twins. METHODS: 196 patients with TTTS treated with laser therapy and 91 uncomplicated MCDA gestations were compared. Neonatal outcomes included respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal death. Risk factors assessed were TTTS, maternal age, maternal body mass index, race, premature prolonged rupture of membranes, stage of TTTS, parity, and gestational age (GA) at delivery. RESULTS: GA at delivery was lower in the TTTS group (31.0 ± 4.6 vs. 33.5 ± 2.4 weeks, p < 0.001). RDS and TTN occurred at higher rates in the TTTS than in the uncomplicated MCDA group. After multivariate logistic regression, the only factor significantly associated with the composite adverse outcome was GA at delivery (OR 0.61; 95% CI: 0.58-0.7). CONCLUSION: TTTS twins treated with FLS are deliver 2.5 weeks earlier than uncomplicated MCDA twins. Respiratory complications were significantly higher in TTTS twins and were mainly the consequence of the early GA at delivery.

Early postnatal cardiac manifestations are associated with perinatal brain injury in preterm infants with twin to twin transfusion syndrome.

Altered hemodynamics associated with twin to twin transfusion syndrome (TTTS) can be manifested in the fetal and neonatal heart. This study evaluated the association between cardiac manifestations immediately after birth and brain injury in preterm infants with TTTS. Medical records of preterm infants who were born at <35 weeks of gestation with TTTS and admitted to the neonatal intensive care unit at Seoul National University Children's Hospital between January 2011 and January 2018 were reviewed. TTTS was prenatally diagnosed and staged according to the Quintero criteria. Echocardiographic findings, brain ultrasound and MRI imaging findings were analyzed. Fifty-three infants were enrolled in this study. Thirty-two infants (60.3%) were treated by fetoscopic laser coagulation. Brain injury developed in 15 infants (28.3%). Hypotension within the first week and immediate postnatal cardiac manifestations were more prevalent in the brain injury group. In the multivariate analysis, acute kidney injury and cardiac manifestations, such as ventricular dysfunction and tricuspid regurgitation, were statistically associated with brain injury in the study population. Immediate postnatal cardiac manifestations, such as ventricular dysfunction and tricuspid regurgitation, can serve as surrogate markers for perinatal hemodynamic disturbance, which are associated with early neonatal brain injury in preterm infants with TTTS.

Spontaneous triplet pregnancy and trap sequence, case report.

BACKGROUND: Spontaneous multiple pregnancies are rare, and the incidence of spontaneous triplet pregnancy is about 1/4000. TRAP (Twin Reversed Arterial Perfusion) sequence has acardiac foetus with non-viable multiple anomalies, and there is a pump foetus which feeds this foetus with placental anastomoses. TRAP sequence phenomena is quite rare in triplet pregnancies. CASE PRESENTATION: The patient who applied to our clinic was 30 years old. Monochorionic diamniotic triplet pregnancy was detected by ultrasonographic examination. First amniotic sac had one foetus (Foetus A). Ultrasonographic evaluation of Foetus A revealed gestational age of 31 weeks, adequate amniotic fluid and no fetal structural anomalies. The second amniotic sac contained 2 foetuses and polyhydromnios. Ultrasonic measurements of Foetus B were consistent with 32 weeks gestational age. Color flow doppler indicated Foetus B was the pump foetus. Foetus C was an acardiac foetus with no sonographic visualization of cranium, thoracic organs or extremities, but abdominal circumference consistent with 28 weeks. Pregnancy was followed conservatively and evaluated regularly by ultrasonography twice a week. When prolonged bradycardia was detected in fetus B at 35 4/7 weeks, emergency cesarean section was performed. Two healthy fetuses weighing 2 kg were delivered each with an 8/10 APGAR score (Appearance, Pulse, Eye Insertion, Activity, Respiration). CONCLUSION: This case was managed without any invasive procedures and demonstrates that treatment of TRAP sequence cases can be individualized considering clinical conditions, the size of the acardia twin and extent of placental venous anastomoses.

Monozygotic Twins with Birth-Weight Differences: Metabolic Health Influenced more by Genetics or by Environment?

BACKGROUND: Low birth-weight (bw), low birth-length (bl), unfavourable intrauterine conditions and post-natal catch-up growth can have an impact on growth and metabolic health later in life. OBJECTIVE: We studied genetically identical twins with intra-twin bw-differences due to twin-twin transfusion syndrome from birth to adolescence and analysed the long-term impact of bw and catch-up growth on metabolic parameters. SUBJECTS AND METHODS: Forty-three postpubertal monozygotic twin-pairs (mean age 17.4 years) were examined. Twenty-two pairs were discordant (intra-twin bw- and/or bl-difference ≥1 SDS) of which 12 (55%) experienced catch-up growth. Auxological parameters and blood pressure were measured, a fasting blood sample was collected and bio-impedance spectroscopy was carried out. RESULTS: Irrespective of differences in birth parameters and postnatal catch-up growth, a significant intra-twin correlation was found for nearly all measured parameters of body composition (skinfold, waist-hip circumference, relative body fat/lean body mass) and metabolic health (total, and low-density lipoprotein-C/high-density lipoprotein-C, Apolipoprotein A and B, C-peptide). As an exception to this, and only for the former smaller twins who showed postnatal catch-up growth, a significantly higher fasting insulin level was found compared to that of the co-twins (mean insulin level: 8.4 vs. 5.7 µIU/mL; p < 0.01). Auxology remained different until adulthood: even in subjects with catch-up growth the former smaller twins were significantly lighter (mean-body mass index-SDS: -0.42 vs. 0.21; p < 0.05) and shorter (mean height-SDS: -0.07 vs. 0.37; p < 0.05) than their co-twins. CONCLUSION: In this special group of monozygotic twins with intra-twin bw-differences and catch-up growth, we found that the genetic background was a more important factor in determining later metabolic health than bw and/or catch-up growth.

Discrepancy in Doppler waveforms between two umbilical arteries in fetuses with absent or reversed end-diastolic flow: A prospective observational study.

PURPOSE: To asses the occurrence of discrepancies between the Doppler waveforms of the left and right umbilical arteries in their paravesical part in fetuses with absent or reversed end-diastolic flow in the free-floating umbilical cord. METHODS: This prospective observational study included pregnant women with fetal growth restriction or twin-to-twin transfusion syndrome. Umbilical arterial Doppler waveforms were obtained from both umbilical arteries in their intra-abdominal paravesical part. Doppler findings were recorded as present end-diastolic flow (PEDF)/absent end-diastolic flow (AEDF); AEDF/AEDF; AEDF/reversed end-diastolic flow (REDF); or REDF/REDF pattern. RESULTS: There were 49 fetuses with AEDF or REDF at the free-floating umbilical cord. Of these, 20 (40.8%) had a discrepancy in Doppler waveforms between the two umbilical arteries, with 14 (28.6%) showing PEDF/AEDF, 17 (34.7%) AEDF/AEDF, 6 (12.2%) AEDF/REDF, and 12 (24.5%) REDF/REDF pattern. CONCLUSION: Doppler waveforms showed discrepancies between the two umbilical arteries in 40.8% of pregnant women with AEDF or REDF in the free-floating umbilical cord. The presence of end-diastolic flow in one umbilical artery cannot exclude the possibility of AEDF in the other.

Assessment of cardiac function in donor and recipient fetuses during a 7-day follow-up after selective laser photocoagulation of communicating vessels due to TTTS.

OBJECTIVES: The aim of the study was to analyze the changes in cardiac function and myocardial contractility of donor and recipient fetuses with twin-to-twin transfusion syndrome (TTTS) subjected to selective laser photocoagulation of the communicating vessels (SLPCV), between and after the procedure. Finally, we verified if fetuses with Quintero's stage I TTTS presented with early impairment of myocardial contractility. MATERIAL AND METHODS: We selected 77 consecutive women with twin pregnancies, whose both fetuses survived at least seven days post-SLPCV. Myocardial contractility of both fetuses was evaluated ultrasonographically, and their myocardial performance indices (Tei-Index values) and shortening fractions (SF) were determined. RESULTS: In donor fetuses, the Tei-Index values for both right and left ventricle remained within the respective reference ranges both before the procedure and during a 7-day follow-up. A significant change in shortening fraction values for the left ventricle in recipient fetuses and the right ventricle of in the donors was observed during a 7-day follow-up. CONCLUSIONS: Comparison of the cardiac parameters of donors and recipients revealed significant differences in Tei-indices during the entire follow-up period. The group with Quintero's I stage TTTS included 74% of recipient fetuses with abnormal Tei-Index values for the right ventricle (mean 0.53).

Maternal and fetal cardiometabolic recovery following ultrasound-guided high-intensity focused ultrasound placental vascular occlusion.

High-intensity focused ultrasound (HIFU) is a non-invasive method of selective placental vascular occlusion, providing a potential therapy for conditions such as twin-twin transfusion syndrome. In order to translate this technique into human studies, evidence of prolonged fetal recovery and maintenance of a healthy fetal physiology following exposure to HIFU is essential. At 116 ± 2 days gestation, 12 pregnant ewes were assigned to control ( n = 6) or HIFU vascular occlusion ( n = 6) groups and anaesthetized. Placental blood vessels were identified using colour Doppler ultrasound; HIFU-mediated vascular occlusion was performed through intact maternal skin (1.66 MHz, 5 s duration, in situ ISPTA 1.8-3.9 kW cm-2). Unidentifiable colour Doppler signals in targeted vessels following HIFU exposure denoted successful occlusion. Ewes and fetuses were then surgically instrumented with vascular catheters and transonic flow probes and recovered from anaesthesia. A custom-made wireless data acquisition system, which records continuous maternal and fetal cardiovascular data, and daily blood sampling were used to assess wellbeing for 20 days, followed by post-mortem examination. Based on a comparison of pre- and post-treatment colour Doppler imaging, 100% (36/36) of placental vessels were occluded following HIFU, and occlusion persisted for 20 days. All fetuses survived. No differences in maternal or fetal blood pressure, heart rate, heart rate variability, metabolic status or oxygenation were observed between treatment groups. There was evidence of normal fetal maturation and no evidence of chronic fetal stress. There were no maternal injuries and no placental vascular haemorrhage. There was both a uterine and fetal burn, which did not result in any obstetric or fetal complications. This study demonstrates normal long-term recovery of fetal sheep from exposure to HIFU-mediated placental vascular occlusion and underlines the potential of HIFU as a potential non-invasive therapy in human pregnancy.

Postnatal Myocardial Function in Monochorionic Diamniotic Twins with Twin-to-Twin Transfusion Syndrome following Selective Laser Photocoagulation of the Communicating Placental Vessels.

BACKGROUND: Monochorionic diamniotic (MCDA) twins are at risk for developing twin-to-twin transfusion syndrome (TTTS) throughout pregnancy. This may lead to myocardial dysfunction in the recipient and/or donor twin that persists beyond delivery. Selective laser photocoagulation of the communicating placental vessels (SLPCV) attempts to mitigate the cardiovascular outcomes. The objective of this study was to characterize early postnatal myocardial performance in MCDA twins with TTTS with and without SLPCV. METHODS: A prospective study was performed of four MCDA twin groups: (1) uncomplicated MCDA twins, (2) MCDA twins with selective fetal growth restriction, (3) MCDA twins with TTTS following SLPCV (TTTS with SLPCV), and (4) MCDA twins with TTTS who did not undergo SLPCV (TTTS without SLPCV). Fifty-four twin pairs were enrolled: 23 uncomplicated MCDA twin pairs, 15 pairs with selective fetal growth restriction, seven TTTS pairs with SLPCV, and seven TTTS pairs without SLPCV. In each group, twin pairs were divided by birth weight into donor (smaller) and recipient (larger) and compared. Echocardiography was performed on day 1, day 2, and between days 5 and 7 of age, and myocardial performance was characterized by speckle-tracking echocardiography-derived left ventricular and right ventricular longitudinal strain (LS) and systolic strain rate (LSR). Longitudinal strain and longitudinal systolic strain rate are expressed as absolute values. RESULTS: Compared with all recipient groups, recipient TTTS without SLPCV infants had lower left ventricular LS (16 ± 3% vs 22%-24%, P < .01) and right ventricular LS (15 ± 5% vs 21%-24%, P < .01) on day 1 that persisted throughout the first week of age. Left ventricular LSR (1.7 ± 0.3 vs 2.3 ± 0.3 sec-1, P < .05) and right ventricular LSR (1.5 ± 0.4 vs 1.7 ± 0.5 sec-1, P < .05) were both lower in the recipient compared with the donor twin in the TTTS without SLPCV group. LS and LSR measurements were similar among all four donor twin groups. CONCLUSIONS: Biventricular performance is diminished in recipient MCDA twins with TTTS who are not treated with SLPCV, highlighting the need for close monitoring of their hemodynamic status during the early neonatal period.

Discordance of umbilical coiling index between recipients and donors in twin-twin transfusion syndrome.

INTRODUCTION: To compare the intertwin umbilical cord coiling in twin-twin transfusion syndrome (TTTS) before fetoscopic laser treatment and to correlate these with Doppler findings in both twins. METHODS: We performed a prospective study using three-dimensional (3D) ultrasound with color Doppler imaging of the umbilical cord in TTTS. Coiling index was measured as a reciprocal value of one complete vascular coil. Ultrasound hypocoiling was thus defined as < 0.2 coils/cm and hypercoiling as > 0.6 coils/cm, respectively. Umbilical artery pulsatility index (PI) and peak systolic velocity, middle cerebral artery peak systolic velocity and ductus venosus PI of flow-velocity waveformes of both twins were measured. RESULTS: We included 65 women in the study. The average gestational age was 21.1 ±â€¯2.7 weeks. In 65 recipients and 56 donors coiling index could be quantified. The median (interquartile range) coiling index of recipient twins was significantly higher than of donors, 0.55 (0.41-0.68) vs. 0.26 (0.2-0.5); P < 0.0001. The proportions of abnormal intertwin coiling were significantly (P = 0.0015) different. Out of 65 recipient with coiling indices evaluation, 1 (1.5%) showed hypocoiled and 27 (41.5%) hypercoiled cords. In contrast, 27 donor twins (48.2%) showed hypocoiled and 5 (8.9%) hypercoiled umbilical cords. There were no significant correlations between the fetal Doppler values and coiling indices. DISCUSSION: Evaluation of umbilical cord coiling index using 3D color Doppler in both twins complicated by TTTS is feasible in both, donors and recipients. Coiling indices differ significantly between recipient and donor twins and do not correlate with Doppler findings.

Beta blocker therapy in recipients of twin-to-twin transfusion syndrome.

Recipients of severe twin-to-twin transfusion syndrome (TTTS) may suffer from low cardiac output caused by myocardial hypertrophy and sudden postnatal drop in preload. Our hypothesis was that selective beta-1 adrenergic blockers improve cardiac function in TTTS recipients with left ventricular outflow tract obstruction. We analysed data from two TTTS recipients treated with esmolol/metoprolol. Despite intense circulatory support, both patients showed severe hypotension and tachycardia before therapy. Echocardiographic findings included hypertrophic ventricles with thickened intraventricular septum, reduced aortic valve velocity time integral (AV-VTI), left ventricular outflow tract obstruction and collapsing ventricles in systole. Beta blocker improved blood pressure as well as AV-VTI, which served as a surrogate parameter for left ventricular stroke volume, reduced heart rate and need for circulatory support. In conclusion, beta blockade may improve left ventricular function in TTTS recipients with low cardiac output due to myocardial hypertrophy.