Randomized Controlled Trial of Twin-Twin Transfusion Syndrome Laser Surgery: The Sequential Trial.

BACKGROUND: Intraoperative blood transfer between twins during laser surgery for twin-twin transfusion syndrome (TTTS) can vary by surgical technique and has been proposed to explain differences in donor twin survival. OBJECTIVE: This trial compared donor twin survival with 2 laser techniques: the sequential technique, in which the arteriovenous communications from the volume-depleted donor to the volume-overloaded recipient are laser-occluded before those from recipient to donor; and the selective technique, in which the occlusion of the vascular communications is performed in no particular order. STUDY DESIGN: A single-center, open-label, randomized controlled trial was conducted in which TTTS patients were randomized to sequential versus selective laser surgery. Nested within the trial, a second trial randomized patients with superficial anastomoses (arterioarterial and venovenous) to ablation of these connections first (before ablating the arteriovenous anastomoses) versus last. The primary outcome measure was donor twin survival at birth. RESULTS: A total of 642 patients were randomized. Overall donor twin survival was similar between the 2 groups (85.6% [274/320] versus 84.2% [271/322], OR 1.12 [0.73-1.73], P=.605). Superficial anastomoses occurred in 27.6% (177/642) of cases. Donor survival was lower in the superficial anastomosis group versus those with only arteriovenous communications (70.6% [125/177] versus 90.3% [420/465], aOR 0.33 [0.20-0.54], P<.001). In cases with superficial anastomoses, donor survival was independent of timing of ablation or surgical technique. The postoperative mean middle cerebral artery (MCA) peak systolic velocity (PSV) was lower in the sequential vs selective group (1.00 ± 0.30 versus 1.06 ± 0.30 MoM, P=.003). Post hoc analyses showed 2 factors that were associated with poor overall donor twin survival: the presence/absence of donor twin preoperative critical abnormal Doppler (CAD) parameters and the presence/absence of arterioarterial anastomoses (AA). Depending on these factors, 4 categories of patients resulted: (1) Category 1 (54%, 347/642), no donor twin CAD + no AA: donor twin survival was 91.2% in the sequential and 93.8% in the selective groups; (2) Category 2 (22%, 143/642), CAD present + no AA: donor survival was 89.9% versus 75.7%; (3) Category 3 (11%, 73/642), no CAD + AA present: donor survival was 94.7% versus 74.3%; and (4) Category 4 (12%, 79/642), CAD present + AA present: donor survival was 47.6% versus 64.9%. CONCLUSION: Donor twin survival did not differ between the sequential versus selective laser techniques, and did not differ if superficial anastomoses were ablated first versus last. The donor twin's postoperative MCA PSV was improved with the sequential versus the selective approach. Post hoc analyses suggest that donor twin survival may be associated with the choice of laser technique according to high-risk factors. Further study is needed to learn if using these categories to guide the choice of surgical technique will improve outcomes. TRIAL REGISTRATION: NCT02122328 with no external funding.

Clinical assessment of the fetal right Quantitative Lung Index.

OBJECTIVES: We have previously described gestational-age-independent sonographic indices to assess fetal lung size in the right and left lungs: The Quantitative Lung Index for the right lung (QLI-R) and for the left lung (QLI-L), respectively. The purpose of this study was to evaluate the clinical cutoff point of the QLI-R to predict pulmonary hypoplasia and neonatal death. MATERIALS AND METHODS: Retrospective assessment of the QLI-R in patients with left-sided congenital diaphragmatic hernia (CDH-L) and other fetal conditions at risk for fetal pulmonary hypoplasia. Cross-section and longitudinal assessment of the behavior of the QLI-R in untreated and treated patients. ROC curve analysis to determine the optimal cutoff point of the QLI-R in predicting neonatal death. RESULTS: One hundred eighteen patients with CDH-L and other fetal conditions at risk for pulmonary hypoplasia had QLI-R measurements done. Seventeen patients were excluded for various reasons. Eleven patients with conditions other than CDH-L but at risk for pulmonary hypoplasia were used for intraclass coefficient measurements of the QLI-R. Ninety patients had CDH-L, of which 78 did not undergo antenatal intervention and in which the cutoff point for pulmonary hypoplasia and neonatal demise was assessed. Stent tracheal occlusion was performed in the remaining 12 patients with CDH-L, in which the behavior of the QLI after surgery was assessed. Analysis of the ICC showed an overall intra-rater reliability of 0.985 (Cronbach's Alpha-based). There was no correlation between gestational age and QLI-R (-0.73, Pearson correlation, p = .72). Twenty-six of the 78 patients (33%) with CDH-L managed expectantly had a neonatal demise. A QLI-R equal to or less than 0.45 was significantly predictive of neonatal demise (area under the curve 0.64, p = .046, sensitivity 77%). Nine of the 12 patients (75%) that underwent tracheal occlusion had neonatal survival. Of these, 10 had serial assessments of the QLI-R after surgery. An increase in the QLI-R of 0.11 was associated with a tendency for neonatal survival (p = .056). CONCLUSION: Our study confirms that the QLI-R is a gestational-age-independent measurement of fetal lung size, with a high degree of reproducibility. In a population of expectantly managed CDH-L patients, a cutoff value of the QLI-R of 0.45 or lower is predictive of neonatal death from pulmonary hypoplasia. The QLI-R can be used to monitor fetal lung growth after tracheal occlusion, and an increase in the QLI-R is suggestive of neonatal survival. Further prospective studies are needed to confirm these findings and to explore the use of the QLI in other populations at risk for pulmonary hypoplasia and consequent neonatal demise.

Fetoscopic demonstration of feto-fetal hemorrhage before actual demise of a monochorionic twin, successful antenatal treatment, and narrative review of the literature.

Feto-fetal hemorrhage (FFH) through placental vascular anastomoses is believed to be responsible for the death or damage of a "second twin" after the demise of a "first twin (co-twin)" in monochorionic twin pregnancies. However, the timing of FFH has been difficult to determine. The resulting anemia in the surviving twin can be suspected by the finding of an elevated middle cerebral artery peak-systolic velocity (MCA-PSV), but this elevation may lag for at least 4 h after the demise of the first twin. Knowledge of the timing of FFH may have important clinical implications, as it may dictate if and when attempts to prevent death or damage to the second twin by delivery or intrauterine fetal transfusion would be warranted. We present a case that supports the notion that FFH occurs before the actual demise of the first twin. A review of the literature was also conducted.

Percutaneous/mini-laparotomy fetoscopic repair of open spina bifida: a novel surgical technique.

Open spina bifida is the most common congenital anomaly of the central nervous system compatible with life. Prenatal repair of open spina bifida via open maternal-fetal surgery has been shown to improve postnatal neurologic outcomes, including reducing the need for ventriculoperitoneal shunting and improving lower neuromotor function. Fetoscopic repair of open spina bifida minimizes the maternal risks while providing similar neurosurgical outcomes to the fetus. The following 2 fetoscopic techniques are currently in use: (1) the laparotomy-assisted approach, and (2) the percutaneous approach. The laparotomy-assisted fetoscopic technique appears to be associated with a lesser risk of preterm birth than the percutaneous approach. However, the percutaneous approach avoids laparotomy and uterine exteriorization and is associated with lesser anesthesia risk and improved maternal postsurgical recovery. The purpose of this article was to describe our experience with a modified surgical approach, which we call percutaneous/mini-laparotomy fetoscopy, in which access to the uterus for one of the ports is done via a mini-laparotomy, whereas the other ports are inserted percutaneously. This technique draws on the benefits of both the laparotomy-assisted and the percutaneous techniques while minimizing their drawbacks. This surgical approach may prove invaluable in the prenatal repair of open spina bifida and other complex fetal surgical procedures.

The quantitative lung index: the left lung.

OBJECTIVE: We have previously described a gestational age-independent sonographic parameter to assess fetal lung growth in the right lung (right quantitative lung index, or QLI-R). The purpose of this study was to develop a similar sonographic parameter to assess the growth of the left lung in the fetus, independent of gestational age, or QLI-L. STUDY DESIGN: A new index, the QLI-L was derived using published formulas for the head circumference (HC) and the area of the base of the left lung (LA), with the corresponding percentiles. RESULTS: Left lung growth can be expressed using the following formula: QLI-L=LAL(HC12)2. The 50th percentile of the QLI-L remained approximately constant at 1.0 for the GA between 16-32 weeks. A small left lung (<1st percentile) was defined as a QLI-L < 0.5. CONCLUSIONS: Fetal left lung growth can be adequately described independent of gestational age using the QLI-L. Further experience is needed to assess the clinical accuracy of the QLI-L in characterizing fetal left lung growth.

Fetal blood gases after in utero carbon dioxide insufflation for percutaneous fetoscopic spina bifida repair.

BACKGROUND: Prenatal repair of open spina bifida via the percutaneous fetoscopic approach does not require maternal laparotomy, hysterotomy, or exteriorization of the uterus. This technique requires intrauterine partial CO2 insufflation. Limited data exist on the physiological effects of CO2 insufflation on human fetuses, with no data on open spina bifida repair performed using the entirely percutaneous fetoscopic surgical technique. OBJECTIVE: Our aim was to examine the effects of intrauterine partial CO2 insufflation on fetal blood gases after percutaneous fetoscopic open spina bifida repair. STUDY DESIGN: This was a prospective study of patients who underwent percutaneous fetoscopic open spina bifida repair from February 2019 to July 2020. Fetal cordocentesis of the umbilical vein was performed in cases with favorable access to the umbilical cord. The umbilical vein cord blood samples were obtained under ultrasound guidance immediately at the conclusion of the open spina bifida repair. Simultaneous maternal arterial blood gas samples were also obtained. The results are reported as median (range). RESULTS: Of the 20 patients who underwent percutaneous fetoscopic open spina bifida repair during the study period, 7 patients (35%) underwent fetal blood sampling. The gestational age at the time of surgery was 27.4 (24.0-27.9) weeks and the operative time was 183 (156-251) minutes. The CO2 exposure time was 122 (57-146) minutes with maximum pressure of 13.5 (12.0-15.0) mm Hg. Fetal umbilical vein results were as follows: pH 7.35 (7.30-7.39), partial pressure of O2 56.2 (47.1-99.9) mm Hg, partial pressure of CO2 43.8 (36.2-53.0) mm Hg, HCO3 23.9 (20.1-25.6) mmol/L, and base excess -2.2 (-4.5 to -0.4) mmol/L. Simultaneous maternal arterial blood gas results were as follows: pH 7.37 (7.28-7.42), partial pressure of O2 187.5 (124.4-405.2) mm Hg, partial pressure of CO2 36.6 (30.7-46.0) mm Hg, HCO3 21.3 (18.0-22.8) mmol/L and base excess -3.2 (-5.9 to -1.8) mmol/L. CONCLUSION: Despite prolonged CO2insufflation of the uterus, fetal umbilical vein pH and base excess values did not approach those associated with potentially pathologic fetal acidemia.

Risks of Preterm Premature Rupture of Membranes and Preterm Birth Post Fetoscopy Based on Location of Trocar Insertion Site.

OBJECTIVE: The objective of this study was to assess whether the location of the trocar insertion site for laser treatment of twin-twin transfusion syndrome was associated with preterm-premature rupture of membranes (PPROM) and preterm birth (PTB). STUDY DESIGN: In this study trocar location was documented in the operating room. Lower uterine segment (LUS) location was defined as any insertion <10 cm vertically from the pubic symphysis. Lateral location was defined as ≥5 cm horizontally from the midline. Patient characteristics were tested against three outcomes: PPROM ≤ 21 days postoperative, PTB < 28 weeks, and PTB < 32 weeks. For each outcome, multiple logistic models were fitted to examine the effect of trocar location, controlling for potential risk factors. RESULTS: A total of 743 patients were studied. Patients with LUS location were twice as likely as those with a more superior location to have PPROM ≤ 21 days (OR = 2.33, 1.12-4.83, p = 0.0236). Patients with both a LUS and Lateral location were over six times more likely to have PPROM ≤ 21 days (OR = 6.66, 2.36-18.78, p = 0.0003). Trocar insertion site was not associated with PTB. CONCLUSION: We found that trocar insertion in the LUS, particularly the lateral LUS, was associated with an increased risk of PPROM.

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

OBJECTIVE: 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). STUDY DESIGN: 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. RESULTS: 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 6.25 mL. 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. CONCLUSIONS: 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.

Amniopatch treatment of iatrogenic preterm premature rupture of membranes (iPPROM) after fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: Amniopatch is a proposed treatment of iatrogenic preterm premature rupture of membranes (iPPROM). We studied characteristics associated with successful amniopatch treatment of iPPROM after fetoscopic laser surgery for twin-twin transfusion syndrome. METHODS: Patients with iPPROM within 15 days of laser surgery treated with an amniopatch were studied. Factors associated with amniopatch success (i.e. cessation of leakage with normalization of amniotic fluid volume) were tested univariately and in multivariate logistic regression models. Continuous variables are expressed as median (range). RESULTS: Of 1124 patients undergoing laser surgery, 19 (1.7%) had iPPROM and subsequent amniopatch. Twelve (63.2%) were successful. Latency in days from iPPROM to delivery was greater in the successful group (114.0 [87.0-141.0]) versus (44.0 [3.9-88.0], p = 0.0005), which translated into greater gestational age (GA) (weeks) at delivery (35.1 [30.9-39.4] versus 28.1 [22.0-31.0], p = 0.0005). The 30-day survival of the affected recipient twin was improved (100% versus 57.1%, p = 0.0361). After multivariate testing, GA < 20 weeks at the time of the amniopatch placement was the only variable that remained associated with successful sealing of the membranes. CONCLUSIONS: Treatment of iPPROM via amniopatch was successful in almost two-thirds of cases and was associated with higher GA at delivery and improved perinatal survival.

Twin-to-Twin Transfusion Syndrome: Definition, Staging, and Ultrasound Assessment.

OBJECTIVE: The purpose of this article is to review the definition of twin-to-twin transfusion syndrome (TTTS) and the sonographic diagnostic assessment of these cases prior to therapy. MATERIALS AND METHODS: The article addresses the terminology used to refer to the condition and describes the systematic ultrasound assessment of the condition, including the ultrasound diagnosis, the staging of the disease, cervical assessment and pre-operative mapping. RESULTS: From an etymologic and medical point of view, the term 'fetofetal transfusion' is more appropriate than 'TTTS'. However, as the latter, and its attendant acronym TTTS, have been widely adopted in the English language, it is impractical to change at this point. TTTS is defined sonographically in the combined presence of a maximum vertical pocket (MVP) of 8 cm or greater in one sac and 2 cm or less in the other sac, regardless of the gestational age at diagnosis. Staging of the condition using the Quintero staging system is practical, reproducible, and accepted. Transvaginal cervical length assessment should be an integral part of the ultrasound evaluation. Pre-operative mapping to anticipate the location of the placental vascular anastomoses and avoid injuring the dividing membrane is also discussed. CONCLUSIONS: The term 'TTTS' can continue to be used in the English medical literature. The condition can be diagnosed and assessed following a systematic ultrasound methodology. The use of such ultrasound methodology breaks the examination into a distinct set of components, assuring a comprehensive examination and proper communication among caregivers.

Laser Treatment of Twin-to-Twin Transfusion Syndrome.

OBJECTIVE: Laser ablation of all placental vascular anastomoses is the optimal treatment for twin-twin transfusion syndrome (TTTS). However, two important controversies are apparent in the literature: (a) a gap between concept and performance, and (b) controversy regarding whether all the anastomoses can be identified endoscopically and whether blind lasering of healthy placenta is justified. The purpose of this article is: (a) to address the potential source of the gap between concept and performance by analyzing the fundamental steps needed to successfully accomplish the surgery, and (b) to discuss the resulting competency benchmarks reported with the different surgical techniques. MATERIALS AND METHODS: Laser surgery for TTTS can be broken down into two fundamental steps: (1) endoscopic identification of the placental vascular anastomoses, (2) laser ablation of the anastomoses. The two steps are not synonymous: (a) regarding the endoscopic identification of the anastomoses, the non-selective technique is based upon lasering all vessels crossing the dividing membrane, whether anastomotic or not. The selective technique identifies and lasers only placental vascular anastomoses. The Solomon technique is based on the theory that not all anastomoses are endoscopically visible and thus involves lasering healthy areas of the placenta between lasered anastomoses, (b) regarding the actual laser ablation of the anastomoses, successful completion of the surgery (i.e., lasering all the anastomoses) can be measured by the rate of persistent or reverse TTTS (PRTTTS) and how often a selective technique can be achieved. Articles representing the different techniques are discussed. RESULTS: The non-selective technique is associated with the lowest double survival rate (35%), compared with 60-75% of the Solomon or the Quintero selective techniques. The Solomon technique is associated with a 20% rate of residual patent placental vascular anastomoses, compared to 3.5-5% for the selective technique (p < .05). Both the Solomon and the selective technique are associated with a 1% risk of PRTTTS. Adequate placental assessment is highest with the selective technique (99%) compared with the Solomon (80%) or the 'standard' (60%) techniques (p < .05). A surgical performance index is proposed. CONCLUSION: The Quintero selective technique was associated with the highest rate of successful ablation and lowest rate of PRTTTS. The Solomon technique represents a historical backward movement in the identification of placental vascular anastomoses and is associated with higher rate of residual patent vascular communications. The reported outcomes of the Quintero selective technique do not lend support to the existence of invisible anastomoses or justify lasering healthy placental tissue.

Decreased Total Placental Mass Found in Twin-Twin Transfusion Syndrome Gestations with Selective Growth Restriction.

INTRODUCTION: We examined placental weight characteristics associated with donor selective intrauterine growth restriction (SIUGR) among patients with twin-twin transfusion syndrome (TTTS) who underwent laser surgery. MATERIALS AND METHODS: Fresh placental specimens were studied. Pregnancies with higher-order multiples, fetal demise, or disrupted or nonsubmitted placental specimens were excluded. Placental characteristics prospectively collected included total placental weight, individual placental weight, and placental share. Data were compared between pregnancies with SIUGR (TTTS + SIUGR group) and those without SIUGR (TTTS-only group). RESULTS: Of 369 consecutive patients who underwent laser surgery for TTTS, 155 (42%) met inclusion criteria: 91 with TTTS + SIUGR and 64 with TTTS-only. Compared to the TTTS-only group, patients in the TTTS + SIUGR group had a lower total placental weight (608 ± 163 vs. 687 ± 224 g, p = 0.012), with a lower donor individual placental weight (237 ± 91 vs. 291 ± 124 g, p = 0.002), but no apparent difference in the individual placental weight of recipient twins (371 ± 109 vs. 396 ± 133 g, p = 0.211). Donor placental share was smaller in those pregnancies affected by SIUGR (38.7 ± 9.6 vs. 42.3 ± 9.8%, p = 0.029). DISCUSSION: TTTS patients with SIUGR had a lower total placental weight and a lower donor individual placental weight compared to those without SIUGR. These findings suggest that differences in donor individual placental weights for SIUGR gestations may not solely be related to differences in placental share.

Endoscopic surgery for the antenatal treatment of myelomeningocele: the CECAM trial.

BACKGROUND: A recent randomized clinical trial named Management of Myelomeningocele Study (MOMS trial) showed that prenatal correction of open spina bifida (OSB) via open fetal surgery was associated with improved infant neurological outcomes relative to postnatal repair, but at the expense of increased maternal morbidity. OBJECTIVE: We sought to report the final results of our phase I trial (Cirurgia Endoscópica para Correção Antenatal da Meningomielocele [CECAM]) on the feasibility, safety, potential benefits, and side effects of the fetoscopic treatment of OSB using our unique surgical technique. STUDY DESIGN: Ten consecutive pregnancies with lumbosacral OSB were enrolled in the study. Surgeries were performed percutaneously under general anesthesia with 3 ports and partial carbon dioxide insufflation. After appropriate surgical positioning of the fetus, the neuroplacode was released with scissors and the skin was undermined to place a biocellulose patch over the lesion. The skin was closed over the patch using a single running stitch. Preoperative, postoperative, and postnatal magnetic resonance imaging were performed to assess hindbrain herniation. Neurodevelopmental evaluation was performed before discharge and at 3, 6, and 12 months. All cases were delivered by cesarean delivery, at which time the uterus was assessed for evidence of thinning or dehiscence. RESULTS: The median gestational age at the time of surgery was 27 weeks (range 25-28 weeks). Endoscopic repair was completed in 8 of 10 fetuses. Two cases were unsuccessful due to loss of uterine access. The mean gestational age at birth was 32.4 weeks with a mean latency of 5.6 weeks between surgery and delivery (range 2-8 weeks). There was 1 fetal and 1 neonatal demise, and 1 unsuccessful case underwent postnatal repair. Of the 7 infants available for analysis, complete reversal of hindbrain herniation occurred in 6 of 7 babies. Three babies required ventriculoperitoneal shunting or third ventriculostomy. Functional motor level was the same or better than the anatomical level in 6 of 7 cases. There was no significant maternal morbidity and no evidence of myometrial thinning or dehiscence. However, surgeries were complicated by premature rupture of membrane and prematurity. CONCLUSION: Our study suggests that the antenatal treatment of OSB using a fetoscopic approach and our unique surgical technique can result in a watertight seal, reversal of the hindbrain herniation, and better than expected motor function. Our technique differs substantially from the classic repair of OSB used in prior open fetal surgery and fetoscopic studies, in which the dura mater is dissected and the defect is closed in multiple layers. Instead, we use a biocellulose patch placed over the lesion and simple closure of the skin. As such, our technique is an alternative to the current paradigms in the antenatal treatment of OSB. Our clinical outcomes are in line with the results of our extensive prior animal work. Maternal benefits of our approach and technique include minimal morbidity and no myometrial legacy. Current limitations of the approach include potential loss of access, premature rupture of membranes, and attendant prematurity. Phase II trials are needed to prevent these complications and to further assess the risks and benefits of our distinct surgical approach and technique.

Selective Reduction Using Intravascular Potassium Chloride Injection after Laser Surgery for Twin-Twin Transfusion Syndrome.

Selective reduction (SR) via intravascular potassium chloride (KCl) injection is contraindicated in monochorionic twins due to the presence of placental vascular communications, which may serve as a conduit for inter-twin passage of KCl or allow exsanguination of the living twin into the demised twin. After successful selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS), the twins' circulatory systems are rendered independent. Theoretically, intravascular KCl injection into one twin after successful SLPCV should not result in passage of the feticidal agent nor cause hemodynamic alterations in the co-twin. We describe 3 cases of 1,069 patients (0.3%) that underwent SLPCV for TTTS between 2003 and 2013 and subsequent SR. SLPCV was successfully completed at 180, 226, and 230 weeks' gestational age for Quintero stages III, IV, and III TTTS, respectively. SR via intravascular KCl injection was later performed at maternal request due to the risk of neurological compromise in one twin at 226, 254, and 236 weeks' gestational age. All co-twins survived after SR, and no neurological sequelae were suspected after birth. Further study is necessary before SR can be routinely considered after laser surgery for TTTS.

Donor catch-up growth after laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: To assess fetal growth after laser surgery for TTTS at the time of prenatal diagnosis, birth, and at 2years of age. DESIGN/METHODS: Growth data were collected from surviving children treated between 2007 and 2010 as part of a study to assess neurodevelopment at 24months (±6weeks) corrected age. Fetal weights were obtained via ultrasound using Hadlock's formula at the time of preoperative assessment for laser surgery. Birth weights were recorded by the staff at the delivering institutions. Weights at 2years corrected age were recorded at the time of neurodevelopmental testing. Weights were converted into percentiles according to standard growth curves. Growth restriction was defined as <10th percentile for given age. Multilevel latent growth curve models in Mplus (twins nested in families) examined weight change over time as a function of donor status, and repeated measures ANOVA was utilized to assess in donor-recipient weight discordance over time for twin pairs. RESULTS: 99 of 206 children (56 of 130 families) were studied. There were no differences between enrolled and non-enrolled patients in donor/recipient status and survival rates, fetal demise, intrauterine growth restriction, Quintero stage, and gestational age of surgery or delivery. 48.5% were donors. The median fetal, birth, and 2-year weights for all twins were 288g, 1.9kg, and 11.8kg, respectively, and the overall prevalence of growth restriction was 28%, 22%, and 3%, respectively. Growth restriction rates at prenatal diagnosis were 56% in donors vs. 2% in recipients (OR=64.3, p<0.001); at birth, 35% vs. 10% (OR=5.0, p<0.01); and at 2years, 6% vs. 0%. Donors showed significant gains in weight percentile (B=13.1, p<0.001) and a significant decrease in growth restriction rates over time (B=-1.6, p<0.001). Weight discordance between donor and recipient pairs also significantly decreased over time (linear F(1,42)=54.34, p<0.001). CONCLUSIONS: After laser surgery for TTTS, donor twins exhibit significant catch-up growth by two years of age.

Abnormal umbilical artery Doppler findings in the recipient twin before laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: In twin-twin transfusion syndrome (TTTS), persistent absent or reversed end-diastolic flow in the umbilical artery is a rare finding in the recipient twin, and the clinical implications of this finding are not well characterized. We sought to study the clinical importance of abnormal umbilical artery Doppler waveforms in recipient twins and determine the perinatal survival of these twins after laser surgery. METHODS: A retrospective study of patients with TTTS treated with laser surgery between 2006 and 2012 was conducted. Recipient twins with absent or reversed umbilical artery end-diastolic flow on preoperative sonography were identified, and clinical and perinatal outcomes were compared to the remaining cohort. Statistical analyses were performed with Fisher exact and χ(2) tests. RESULTS: Of 369 consecutive TTTS cases, 14 (3.8%) had absent or reversed umbilical artery end-diastolic flow in the recipient twin. The rate of hydrops was higher in this group compared to those without absent or reversed flow (35.7% [5 of 14] versus 10.1% [36 of 355]; P = .0125). The rate of recipient twin growth restriction was also higher in the absent or reversed flow group (28.6% [4 of 14] versus 3.9% [14 of 355]; P = .0029). There was an increased rate of recipient fetal demise within 24 hours after surgery in those with absent or reversed flow (21.4% [3 of 14] versus 2.5% [9 of 355]; P = .0078), although there was no statistical difference in 30-day survival between the groups (78.6% [11 of 14] versus 89.9% [319 of 355]; P = .1751). CONCLUSIONS: Doppler findings of absent or reversed umbilical artery end-diastolic flow are rare in recipient twins. Although immediate post-laser surgery survival is relatively decreased in this group, overall perinatal survival rates appear to be favorable.

Pre-Operative Twin Anemia/Polycythemia in the Setting of Twin-Twin Transfusion Syndrome (TTTS).

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS) are classified as distinct clinical disorders associated with unbalanced blood flow through placental vascular communications. Typically, TAPS placentas demonstrate few <1 mm arteriovenous (AV) communications, and at fetoscopy the twins are visibly pale and plethoric. MATERIALS AND METHODS: In a cohort of TTTS patients who underwent laser surgery, those with preoperative findings suggestive of anemia/polycythemia (AP) were compared to those with TTTS alone. AP was defined as middle cerebral artery peak systolic velocity in one twin >1.5 multiples of the median (MoM), and <1.0 MoM in the other. RESULTS: Of 369 TTTS patients, 9 (2.4%) met criteria for preoperative AP. The mean number (±SD) of AV communications in the TTTS + AP group was 5.6 ± 5.7, compared with 8.8 ± 4.8 in the TTTS-alone group (p = 0.013). Five TTTS + AP patients (56%) had a few thin AV communications (mean 2.8 ± 1.6); all 5 had visibly pale and plethoric twins. The remaining 4 (44%) had large or numerous anastomoses (mean 10.5 ± 6.8); none had fetal skin color discordance. DISCUSSION: Preoperative AP affected 2% of TTTS patients. Of these, approximately half had placental and skin color findings typically reported with isolated TAPS.

Perinatal survival in cases of twin-twin transfusion syndrome complicated by selective intrauterine growth restriction.

OBJECTIVE: To evaluate the impact of selective intrauterine growth restriction (SIUGR) on monochorionic multiples treated with selective laser photocoagulation of communicating vessels (SLPCVs) for twin-twin transfusion syndrome (TTTS). METHODS: Perinatal survival was compared among TTTS patients with and without SIUGR. The TTTS + SIUGR group was defined as TTTS patients with donor twin weight <10th percentile. Multivariable logistic regression analyses identified factors associated with 30-day survival. RESULTS: Of 369 patients, 65% (N = 241) had TTTS + SIUGR. Thirty-day donor twin survival for the TTTS-only group was 84% versus 75% in the TTTS + SIUGR group (p = 0.0348). Stage III donor involved (stage III donor, donor/recipient) TTTS + SIUGR patients (N = 110) had 66% 30-day donor survival. Multivariable logistic regression demonstrated that the TTTS-only group was twice as likely to achieve donor survival compared to the TTTS + SIUGR group (OR 2.01, 95% CI 1.11-3.66, p = 0.0214). In the TTTS + SIUGR group, patients not classified as stage III donor-involved were twice as likely to achieve donor survival as stage III donor-involved patients (OR 2.02, 95% CI 1.10-3.71, p = 0.0226). CONCLUSIONS: SIUGR, present in two-thirds of TTTS patients, was a risk factor for decreased donor survival. Patients with donor SIUGR and umbilical artery persistent or reversed end-diastolic flow (Quintero Stage III Donor-involved) were especially at risk.