Fetuses undergo major surgical stress as well as fluid shifts secondary to both twin-twin transfusion (TTTS) as well as the fetoscopic surgery for treatment of TTTS. While the pathophysiology of TTTS is understood, the acute metabolic changes that fetuses experience from fetoscopic surgery are not. We sought to evaluate the changes in recipient metabolomic profile secondary to TTTS surgery. Amniotic fluid was collected at the beginning and end of four TTTS surgical cases performed from 12/2022-2/2023. Samples were immediately processed and evaluated via NMR-based Metabolomics Facility protocol. In univariate analysis, 12 metabolites (glucose, lactate, and 10 key amino acids) showed statistically significant changes between the beginning and end of the surgery. Among these, 11 metabolites decreased at the end, while only lactate increased. Supervised oPLS-DA modeling revealed pyruvate and lactate as the two metabolites most impact on the variance between cases, and that 40% of metabolomic changes could be attributed directly to the timing that the sample was taken (i.e., if pre- or postoperatively). These results indicate significant metabolic changes in the recipient twin during fetoscopic surgery for TTTS. These findings of decreased glucose, increased lactate, and decreased amnio acids would indicate increased catabolism during surgery. This study raises questions regarding optimal maternal and fetal nutrition during surgery and if nutritional status could be optimized to further improve twin survival during fetoscopic surgery.

BACKGROUND: Fetoscopic laser coagulation of placental anastomoses reverses the pathological process in twin-to-twin transfusion syndrome, thereby increasing survival, but there are a paucity of studies addressing long-term neurodevelopmental outcome of survivors. This study aimed to ascertain the presence of neurodevelopmental disabilities in child survivors of monochorionic pregnancies managed by placental laser photocoagulation in the Australian state of Victoria.
METHODS: All pregnancies undergoing placental laser photocoagulation with the Victorian Fetal Therapy Service between 2006-2017 were included. Information on each surviving child, including demographics, perinatal course, and developmental progress was collected from parents, and consent was sought to complete the Child Behaviour Checklist. Interviewers evaluated whether this information was consistent with a diagnosis of any of 14 neurodevelopmental conditions. A three-tiered outcome measure was allocated for each child: (1) unimpaired or developmentally normal, (2) mild or moderate neurological impairment, or (3) severe neurological impairment. Clinical predictors for adverse outcome were identified.
RESULTS: Of 116 pregnancies (113 twin, 3 triplet), 96 (83%) resulted in 1 + surviving fetuses. 57/113 (50%) twin pregnancies resulted in 2 survivors, 36 (32%) in 1 survivor, and 20 (18%) in no survivors. Of the 235 fetuses, 154 (65.5%) survived to follow-up. Survival increased from 59% in 2006-2008 to 73% in 2015-2017. 90/154 (58%) survivors were followed up at a mean age of 7.5 [SD 3.0] years. Based on parental interview and Child Behaviour Checklist data, 28/90 (31%) participants were assessed as having neurodevelopmental impairment, 27 of mild-moderate severity and 1 severe. Speech/language disorders, attention deficit (hyperactivity) disorders, and fine motor impairment were most common. Neonatal length of stay conferred the highest risk of impairment.
CONCLUSIONS: Substantial variation exists between fetal therapy services in the type and length of neonatal follow-up following fetoscopic laser coagulation, contributing to a lack of data on long-term outcomes. The findings from this study support increasingly urgent calls to undertake systematic and sustained follow-up of fetoscopic laser coagulation survivors until school age. Information from this study may assist parents in their decision-making when offered fetal surgery. Importantly, it highlights a group for targeted surveillance and early intervention.

UNASSIGNED: Monochorionic diamniotic (MCDA) twin pregnancies are considered high-risk for several reasons, especially the risk of twin-to-twin transfusion syndrome (TTTS). Renal artery Doppler (RAD) is reported as a useful tool for predicting oligohydramnios in singleton pregnancies. We aimed to compare the RAD indices between MCDA twins with and without TTTS.
UNASSIGNED: In this case-control study, all pregnant women aged 18-38 years, with gestational age ≥ 18 weeks, who were referred to two Prenatal Clinics, Alzahra and Beheshti Educational Hospitals, affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, October 2020-March 2022 were enrolled; the women with MCDA twin pregnancies complicated by TTTS (case group, n = 12) and without TTTS (control group, n = 24). For each twin, biometric analysis, fetal weight, and Doppler study of fetal arteries, including RAD, middle cerebral artery (MCA), umbilical artery, and ductus venosus were performed. Peak systolic velocity, Pulsatility index (PI), resistance index (RI), and systole/diastole (S/D) were measured for all arteries.
UNASSIGNED: The donors of the case group had a lower mean MCA S/D (4.48 ± 1.89) than the control group (6.48 ± 1.97) (P = 0.01) and higher mean umbilical parameters, including PI, RI, and S/D (P < 0.05). The recipients of the case group had a lower mean renal PI than the control (P = 0.008) and lower mean MCA PI, RI, and S/D (P < 0.05). The donor group had a higher mean umbilical RI and S/D than the recipient twin, while the mean fetal weight of the recipient group was higher (P < 0.05).
UNASSIGNED: Comparing the RAD parameters between the twins with and without TTTS in the present study did not identify significant results, which rejected the primary hypothesis. Among all RAD parameters, the only significant difference observed in the present study was the lower RAD PI in RT, which cannot suggest this measurement as a valuable tool for the prediction of TTTS in MCDA twins. Therefore, the results of the present study failed to show the additional value of RAD, compared with the conventional Doppler examination of fetal arteries. Further studies are required to prove this conclusion.

Twin anemia polycythemia sequence (TAPS) is a consequence of unequal sharing of red blood cells between monochorionic twins resulting in anemia in the donor and polycythemia in the recipient twin. Prenatally TAPS can occur spontaneously or complicate incomplete laser surgery for twin transfusion syndrome. While there may be clinical overlap with twin transfusion syndrome or selective fetal growth restriction, diagnosis relies on Doppler measurement of middle cerebral artery peak systolic velocities. Significantly discordant velocities are diagnostic, while severity staging is based on signs of cardiovascular compromise. Conservative management, fetoscopic laser coagulation, selective twin reduction, fetal blood and exchange transfusion, and delivery may be selected guided by the gestational age of diagnosis, the severity of the condition, the likelihood of success, and the patients\' priorities. Prenatal curative treatment that minimizes the risk for prematurity and residual morbidity at birth is most likely to offer the greatest short-term and long-term benefits.

OBJECTIVE: We aimed to investigate the prevalence and clinical outcomes of twin-to-twin transfusion syndrome (TTTS) with proximate cord insertions.
METHODS: This was retrospective cohort study of TTTS cases managed at single fetal center between 2012 and 2020. Presence of proximate cord insertions was defined as a distance of equal or less than 4 cm between placental cord insertions that was recorded based on sonographic and fetoscopic examinations. Clinical outcomes were investigated compared to unmatched cohort and to 1:2 matched controls using preoperative variables including Quintero staging, selective fetal growth restriction, anterior placenta, preoperative cervical length, and gestational age at fetal intervention. Systematic review and meta-analysis were conducted following PRSMA guidelines through searching PubMed, Scopus, CINAHL, and Medline databases from inception until January 2021.
RESULTS: The prevalence of proximate cord insertions in monochorionic placentas with TTTS was 2% (5/246). All 5 cases were managed by fetoscopic laser surgery (FLS). Procedure time was significantly longer (mean: 61.4 min in proximate cord vs. 37.5 min in nonproximate cord, p < 0.001), and amnioinfusion was significantly more common (100% in proximate cord vs. 43% in nonproximate cord, p = 0.01). Perinatal survival and neonatal outcomes were not different between groups. Similar findings were seen following 1:2 control matching. Systematic review yielded total of 19 case reports of which different management options were applied including FLS (n = 13), amniodrainage (n = 3), and selective reduction (n = 3). Clinical outcomes results were mixed and inconsistent. FLS was described as technically challenging and residual anastomosis was common. Overall fetal and neonatal survival following FLS was 85% and 80%, respectively.
CONCLUSIONS: Presence of proximate cords in TTTS cases poses serious technical challenges even for highly experienced surgeons. Feasibility should be only determined by fetoscopic examination.

Clinically significant extrauterine twin-twin transfusion syndrome in conjoined twins is rare and carries a high risk of perinatal mortality. The ensuing postnatal imbalance in circulation across connecting vessels results in hypovolemia in the donor and hypervolemia in the recipient. Data on management and treatment are sparse especially in the setting of a single ventricle congenital heart defect. We present a case of a pair of omphalopagus conjoined twins, one with a single ventricle physiology (Twin B), who developed twin-twin transfusion syndrome shortly after birth. The resulting pathophysiology in the setting of a single ventricle congenital heart defect created added layers of complexity to their management and expedited surgical separation. Shunting from Twin B to Twin A-with an anatomically normal heart-resulted in mal-perfusion and rapid deterioration jeopardizing the health of both twins. In the preoperative course, steps taken to medically optimize the twins prior to surgery and the anesthetic considerations are detailed in this report.

Amyoplasia is a very specific, nongenetic clinically recognizable form of arthrogryposis, representing about one-third of individuals with arthrogryposis surviving the newborn period. There is a markedly increased number of individuals with Amyoplasia who are one of monozygotic (MZ) twins, with the other twin being normal. Thus, it would appear that Amyoplasia is definitely associated with and may be caused by an MZ twinning event. The twin-twin transfusion seen in MZ twins could play an etiologic role in producing Amyoplasia. In this article, Amyoplasia twinning is compared to twinning in other forms of arthrogryposis. The accompanying paper examines various types of MZ twinning (Hall, 2021). Amyoplasia is primarily associated with spontaneous MZ twinning.

Myocardial infarction type 2 (MI type 2) is an elevation of cardiac biomarkers in a physiologically stressful state leading to demand-supply mismatch of oxygen. This type of myocardial infarction is commonly seen in hospitalized patients. Since the introduction of clear definition, diagnostic criteria and International Classification of Disease (ICD) codes, the diagnosis has become increasingly common. There still remains plenty to learn about MI type 2 especially prevention and treatment strategies. Studies have shown that there is increased mortality and morbidity associated with MI type 2 when compared to MI type 1, and there may be benefit in having a multi-disciplinary approach including cardiology when treating such patients. Secondary prevention therapies may also play a role in decreasing adverse events from MI type 2. However, randomized control trials are insufficient, and results of studies are cautiously interpreted. In this article we have assessed the current evidence on MI type 2 and the gap in literature that will potentially be the focus of future analyses.

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.

Cardiovascular anomalies are more common in monochorionic twins, especially with twin-twin transfusion, compared to other twin types and to singletons. Because previous studies are based on fetal and neonatal echocardiography, more information is needed to study prevalence of cardiac anomalies in twin miscarriages, stillbirths, and children after the immediate neonatal period.
With specific attention to cardiac anomalies, we reviewed the medical records of 335 selected liveborn twin pairs from the Marshfield Clinic Twin Cohort (enriched for twin-twin transfusion) and all twins (175 pairs) identified in the Wisconsin Stillbirth Service Program cohort of late miscarriages and stillbirths.
Structural cardiac defects occurred in 12% of liveborn monochorionic twin infants and 7.5% of stillborn infants with twin-twin transfusion compared to only 2% of liveborn dizygotic twins and no stillborn dizygotic infants. The most common cardiac lesion in liveborn twins was ventricular septal defect, which was usually isolated and discordant, preferentially affecting the smaller twin in monochorionic pairs. Among stillborn and miscarried monochorionic twins, the most common cardiac lesion was acardia.
Monochorionic twins, particularly those with TTT, are at increased risk for a spectrum of structural cardiac malformations which we suggest may be related to asymmetry of the inner cell mass resulting in a smaller poorly perfused twin. In severe cases, limited cardiac and circulatory development in the affected twin leads to acardia. In less severe cases, the smaller infant has deficient septal growth that sometimes results in ventricular septal defect.