Cardiac adaptation and malformation in twin-twin transfusion syndrome and selective fetal growth restriction: A systematic review.

OBJECTIVES: This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs). METHODS: Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta-analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins. RESULTS: In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co-occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta-analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5-4.9) for TTTS and 2.2 (95%CI: 1.3-3.5) for sFGR compared with uncomplicated MC twins. CONCLUSIONS: This study highlights the well-documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long-term consequences.

Neurodevelopmental outcome in complicated twin pregnancy: prospective observational study.

OBJECTIVE: Twin pregnancy is associated with increased perinatal mortality and morbidity, but long-term neurodevelopmental outcome remains underinvestigated. The primary objective of this study was to investigate the incidence of adverse neurodevelopment after 1 year of age in complicated monochorionic diamniotic (MCDA) twin pregnancies compared with uncomplicated twin pregnancies. METHODS: This was a prospective cohort study conducted at St George's University Hospital NHS Foundation Trust, London, UK. Women with a twin pregnancy culminating in at least one surviving child, aged between 12 and 60 months (corrected for prematurity) at the time of assessment, were invited to complete the relevant Ages and Stages Questionnaire® version 3 (ASQ-3) test. The two study groups were: (1) complicated MCDA twin pregnancies, including those with twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, twin reversed arterial perfusion sequence and/or single intrauterine demise; and (2) uncomplicated MCDA and dichorionic diamniotic twin pregnancies. The primary outcome measure was an abnormal ASQ-3 score, defined as a score of more than 2 SD below the mean in any one of the five domains. Mixed-effects multivariable logistic regression analysis was performed to determine whether a complicated MCDA twin pregnancy was associated independently with an abnormal ASQ-3 score. RESULTS: The study included 174 parents who completed the questionnaire for one or both twins; therefore, 327 ASQ-3 questionnaires were available for analysis. Of those, 117 (35.8%) were complicated MCDA twin pregnancies and 210 (64.2%) were controls. The overall rate of an abnormal ASQ-3 score in children born of a complicated MCDA twin pregnancy was nearly double that of those from uncomplicated twin pregnancies (14.5% vs 7.6%; P = 0.056). Children born of a complicated MCDA twin pregnancy had a significantly higher rate of impairment in the gross-motor domain compared with the control group (8.5% vs 2.9%; P = 0.031). Complicated MCDA twin pregnancies that underwent prenatal intervention had a significantly higher rate of abnormal ASQ-3 score compared with those that did not undergo prenatal intervention (28.1% vs 1.7%; P < 0.001). On multilevel logistic regression analysis, complicated MCDA twin pregnancy was an independent predictor of abnormal ASQ-3 score (adjusted odds ratio, 3.28 (95% CI, 3.27-3.29); P < 0.001). CONCLUSIONS: This study demonstrates that survivors of complicated MCDA twin pregnancies have a higher rate of adverse neurodevelopmental outcome, independently of prematurity. Long-term neurodevelopmental follow-up in these pregnancies can ensure timely and optimal management of those affected. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome, natural history, and risk factors for fetal death: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the natural history of selective intrauterine growth restriction in monochorionic twin pregnancies based on the Gratacós classification, including progression of, improvement in, or stability of umbilical artery Dopplers and progression to twin-to-twin transfusion syndrome or twin anemia polycythemia syndrome. We also aimed to investigate risk factors for smaller twin demise. DATA SOURCES: A systematic search was performed to identify relevant studies published in English up to June 2022 using the databases PubMed, Scopus, and Web of Science STUDY ELIGIBILITY: We used retrospective and prospective studies published in English that reported on selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome. STUDY APPRAISAL AND SYNTHESIS METHODS: Articles that investigated selective intrauterine growth restriction progression and outcomes by umbilical artery Doppler end-diastolic flow (Gratacós classification) were included. Type I included selective intrauterine growth restriction cases with positive end-diastolic flow, type II included those cases with persistently absent end-diastolic flow, and type III included cases with intermittent absent or reversed end-diastolic flow. Pregnancies in which a diagnosis of twin-to-twin transfusion syndrome or twin anemia polycythemia sequence was made before the diagnosis of selective intrauterine growth restriction were not included in the analysis. A random effects model was used to pool the odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 17 studies encompassing 2748 monochorionic pregnancies complicated by selective intrauterine growth restriction were included in the analysis. The incidence of stable, deteriorating, or improving umbilical artery Dopplers in type I cases was 68% (95% confidence interval, 26-89), 23% (95% confidence interval, 7-40), and 9% (95% confidence interval, 0.0-100), respectively. In type II cases, the incidence was 40% (95% confidence interval, 18-81), 50% (95% confidence interval, 23-82), and 10% (95% confidence interval, 4-37), respectively, and in type III cases, the incidence was 55% (95% confidence interval, 2-99), 23% (95% confidence interval, 9-43), and 22% (95% confidence interval, 6-54), respectively. The risk for progression to twin-to-twin transfusion syndrome was comparable between type I (7%) and type III (9%) cases and occurred in 4% (95% confidence interval, 0-67) of type II cases with no significant subgroup differences. Progression to twin anemia polycythemia syndrome was highest in type I cases (12%) and comparable between type II (2%) and III (1%) cases with no significant subgroup differences. Risk factors for smaller twin demise were earlier gestational age at diagnosis (mean difference, -2.69 weeks; 95% confidence interval, -4.94 to -0.45; I2, 45%), larger intertwin weight discordance (mean difference, 34%; 95% confidence interval, 1.35-5.38; I2, 28%), deterioration of umbilical artery Dopplers for each of type II and III cases (odds ratio, 3.05; 95% confidence interval, 1.36-6.84; I2, 24%; and odds ratio, 4.5; 95% confidence interval, 2.31-8.77; I2, 0.0%, respectively), and absent or reversed ductus venosus a-wave for each of type II and III cases (odds ratio, 3.35; 95% confidence interval, 2.28-4.93; I2, 0.0%; and odds ratio, 2.36; 95% confidence interval, 1.08-5.13; I2, 0.0%, respectively). Progression to twin-to-twin transfusion syndrome was not significantly associated with smaller twin demise for each of type II and III selective intrauterine growth restriction cases. CONCLUSION: These findings improve our understanding of the natural history of the types of selective intrauterine growth restriction and of the predictors of smaller twin demise in type II and III selective intrauterine growth restriction cases. The current data provide vital counseling points and support the need for modifications of the current selective intrauterine growth restriction classification system to include the variations in umbilical artery and ductus venosus Dopplers to better identify a cohort that might benefit from fetal intervention for which future multicenter prospective randomized trials are needed.

Twin Anemia-Polycythemia Sequence (TAPS): From Basic Research to Clinical Practice.

Twin pregnancy is associated with an increased risk of perinatal and maternal complications, and early establishment of the chorionicity type defines this risk. In monochorionic (MC) pregnancies, the fetuses share the same placental mass and exhibit vascular anastomoses crossing the intertwin membrane, and the combination and pattern of anastomoses determine the primary clinical picture and occurrence of future complications. Twin Anemia-Polycythemia Sequence (TAPS) was first described in 2006 after fetoscopic laser surgery in twin-to-twin transfusion syndrome (TTTS) twins, and in 2007, the first spontaneous cases were reported, recognizing TAPS as an individualized vascular identity in fetofetal transfusion syndromes. There are two types of TAPS: spontaneous (3-5%) and iatrogenic or postlaser (2-16%). TAPS consists of small diameter arteriovenous anastomoses (<1 mm) and low-rate, small-caliber AA anastomoses in the absence of amniotic fluid discordances. There are certain antenatal and postnatal diagnostic criteria, which have progressively evolved over time. New, additional secondary markers have been proposed, and their reliability is being studied. The best screening protocol for TAPS in MC twins is still a matter of debate. This review provides a survey of the relevant literature on the epidemiology, vascular pathophysiology, underlying hemodynamic factors that regulate mismatched vascular connections, and diagnostic criteria of this condition. The aim is to increase awareness and knowledge about this recently identified and frequently unrecognized and misdiagnosed pathology.

Association between fetal sex and pregnancy outcomes among women with twin pregnancies: a multicenter cross-sectional study.

PURPOSE: To examine the frequency and to what extent fetal sex is associated with pregnancy outcomes among twin pregnancies, stratified by chorionicity. METHODS: This registry-based multicenter cross-sectional study was conducted using the Japan Society of Obstetrics and Gynecology perinatal database between 2007 and 2016. The sample population was restricted to women with twin pregnancies. The main pregnancy-related outcomes included preterm birth, very preterm birth, extremely preterm birth, preeclampsia, twin-to-twin transfusion syndrome (TTTS), and selective intrauterine growth restriction (s-IUGR). Birth weight, small for gestational age (SGA), and fetal death were also investigated. RESULTS: The primary analysis was performed based on 37,953 women, including 23,804 women with dichorionic diamniotic (DD) twins and 14,149 women with monochorionic diamniotic (MD) twins. Women with male/male DD twins had a significantly higher risk of preterm birth (adjusted risk ratio [aRR]: 1.07, 95% confidence interval [CI]: 1.03-1.10) and a lower risk of preeclampsia (aRR: 0.74, 95% CI: 0.62-0.88) than women with female/female DD twins. Women with male/male MD twins also had a significantly higher risk of preterm birth (aRR: 1.06, 95% CI: 1.04-1.09) than women with female/female MD twins. Risks of preeclampsia, TTTS, and s-IUGR did not differ by sex among MD pregnancies. Male SGA risk was significantly higher among male/male twins than among male/female DD twins. Among MD twins, risks of SGA and fetal death were significantly higher in male/male fetuses. CONCLUSIONS: This study demonstrated significant associations between fetal sex and several pregnancy outcomes in twin pregnancies, some of which differed by chorionicity.

Pregnancy outcomes following early fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome at 16 weeks' gestation.

BACKGROUND: Ample evidence supports fetoscopic laser photocoagulation of placental anastomoses as a first-line treatment for twin-to-twin transfusion syndrome, but little is known about the outcomes following procedures conducted in the early second trimester. OBJECTIVE: This study aimed to evaluate perinatal outcomes following early fetoscopic laser placental photocoagulation performed for twin-to-twin transfusion syndrome at 16 weeks' gestation. STUDY DESIGN: This retrospective review included monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome necessitating fetoscopic laser photocoagulation at a single tertiary center from 2012 to 2021. The 2 cohorts were defined as cases undergoing laser surgery at 16+0/7 to 16+6/7 weeks' gestation (early laser group) and those undergoing laser surgery ≥17 weeks' gestation (standard laser group), respectively. Primary outcomes included rates of immediate chorioamniotic membrane separation, preterm premature rupture of membranes, and clinical chorioamnionitis. Secondary outcomes included twin survival rates at birth and 30 days of life. Outcomes were compared between cohorts with a P value of <.05 denoting statistical significance. RESULTS: A total of 343 cases were included (35 early laser participants and 308 standard laser participants). The early laser group typically had higher Quintero staging at the time of the procedure. Following intervention, the early laser group had significantly higher rates of chorioamniotic separation than the standard laser group (34.3% vs 1.3% of cases; P<.001) and higher rates of preterm prelabor rupture of membranes (45.7% vs 25.0%; P=.009) and chorioamnionitis (11.4% vs 1.3%; P=.005). Even after adjustment for higher Quintero staging in the early laser group, twin survival was not significantly different between study groups. CONCLUSION: Early laser surgery for twin-to-twin transfusion syndrome performed at 16 weeks' gestation is associated with significantly higher rates of chorioamniotic separation, preterm rupture of membranes, and chorioamnionitis. However, twin survival does not seem to be negatively impacted following early laser surgery.

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis.

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n = 671 undergoing Solomon and n = 993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: -1.167; 95% credible interval [CrI]: -2.01, -0.33; p = 0.021; I2 : 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p = 0.012; I2 : 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: -0.43, 1.49; p = 0.131; I2 : 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption.

Perinatal and long-term outcome of endoscopic laser surgery for twin-twin transfusion syndrome with and without selective fetal growth restriction: A retrospective cohort study.

OBJECTIVE: Report survival rates, neonatal mortality and morbidity and long-term outcomes of monochorionic (MC) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) or TTTS plus selective fetal growth restriction (sFGR) treated by endoscopic laser surgery. METHODS: Retrospective cohort study including 149 MC twin pregnancies complicated by TTTS or TTTS plus sFGR.Medical records were reviewed for survival rates, neonatal mortality, neonatal morbidity and long-term outcomes at 2 and 6 years of age. RESULTS: Survival of both babies was higher in the TTTS group than in the TTTS plus sFGR group (72.9%vs.54.8%); survival of at least one baby was similar in the two groups (90.7% and 88.1%). The incidence of severe neurological disability was not significantly different between TTTS and TTTS plus fetal growth restriction group at both stages, 1.9% versus 2.3% (p-value = 1) and 3.4%vs6.1% (p-value = 0.31). Multivariable analysis demonstrated that intact neurological outcome at 2 years of age was related with gestational age (GA) at birth and z score birthweight (Z BW), and at 6 years of age with GA at birth, Z BW and TTTS stage4. sFGR or abnormal brain findings at neonatal ultrasound were not related with impaired neurological outcome at two or 6 years of age. CONCLUSIONS: In pregnancies with TTTS and TTTS plus sFGR survival of at least one baby and long-term neurological outcome are comparable between both groups.

Fetal and neonatal brain injury in twins complicated by twin anemia polycythemia sequence.

OBJECTIVES: To determine the rate of fetal and neonatal brain lesions and define risk factors for such lesions in pregnancies complicated by Twin Anemia Polycythemia Sequence (TAPS). METHODS: A retrospective cohort study of monochorionic twin pregnancies which were diagnosed with TAPS in a single tertiary medical center between 2013 and 2021. Pregnancies were followed with fetal brain neurosonogram every 2 weeks and fetal brain MRI (magnetic resonance imaging) was performed when indicated at 28-32 weeks of gestation; post-natal brain imaging included neonatal brain ultrasound. Pregnancies with pre- and post-natal brain lesions were compared to those without such findings. RESULTS: Overall, 23 monochorionic diamniotic pregnancies were diagnosed with TAPS over the study period resulting in perinatal survival of 91.3% (42/46). In 6/23 (26%) pregnancies and 7/46 (15.2%) fetuses pre- or post-natal brain lesions were detected, of whom five were the polycythemic twins and two were the anemic twins. Brain findings included intra-cerebral hemorrhage and ischemic lesions and were diagnosed prenatally in 6/7 (85.7%) cases. No risk factors for severe brain lesions were identified. CONCLUSIONS: TAPS may place the fetuses and neonates at increased risk for cerebral injuries. Incorporation of fetal brain imaging protocols may enhance precise prenatal diagnosis and allow for accurate parental counseling and post-natal care.

Incidence, prognosis, and perinatal outcomes of and risk factors for severe twin-twin transfusion syndrome with right ventricular outflow tract obstruction in the recipient twin after fetoscopic laser photocoagulation.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is the most frequently encountered congenital heart disease in patients with twin -twin transfusion syndrome (TTTS) and is especially prevalent in the recipient twin. In this retrospective study, we evaluated the incidence, prognosis, postnatal management, and perinatal outcomes of and risk factors for RVOTO in the recipient twin in severe TTTS cases which diagnosed before 26 weeks after fetoscopic laser photocoagulation (FLP) at a single center in Taiwan. METHODS: RVOTO was diagnosed using fetal or postnatal echocardiography. The fetal outcomes evaluated were perinatal survival rate, neonatal brain image anomalies rate, gestational age at delivery, and birth weight. RESULTS: Total 187 severe TTTS cases were included; 14 (7.49%) had a recipient twin with RVOTO (12 cases of pulmonary stenosis and 2 of pulmonary atresia). Of these 14 cases, 3 (21.4%) demonstrated improvements in outflow obstruction after FLP, and 11 (78.6%) resulted in perinatal survival. Of the 11 survivors, 5 (45.5%) received transcatheter balloon valvuloplasty to alleviate the RVOTO. The perinatal survival rate, gestational age at delivery, neonatal brain image anomaly rate, and birth weights did not significantly differ between the groups in which the recipient twin had versus did not have RVOTO. Generally, the recipient twin had RVOTO received FLP at a younger gestational age (in weeks; 19.3 ± 2.4 vs. 20.7 ± 2.6, p = 0.048) and had a higher percentage of cases at Quintero stage IV (50.0% vs. 12.1%, p < 0.001) than those in which the recipient twin did not have with RVOTO. Using logistic regression, we discovered that FLP at a younger gestational age (p = 0.046, odds ratio = 0.779) and TTTS at Quintero stage IV (p = 0.001, odds ratio = 7.206) were risk factors for the recipient twin developing RVOTO after FLP in severe TTTS cases. CONCLUSIONS: The post-FLP perinatal outcomes of cases of severe TTTS in which the recipient twin had versus did not have RVOTO were comparable in this study, which may have been due to the similar gestational ages at delivery and strong influence of high Quintero stages (stages III and IV).

Efficacy of long-term indomethacin therapy in prolonging pregnancy after fetoscopic laser surgery for twin-to-twin transfusion syndrome: a collaborative cohort study.

OBJECTIVE: To evaluate the efficacy of long-term indomethacin therapy (LIT) in prolonging pregnancy and reducing spontaneous preterm birth (PTB) in patients undergoing fetoscopic laser surgery (FLS) for the management of twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Collaborative multicentre study. POPULATION: Five hundred and fifty-seven consecutive TTTS cases that underwent FLS. METHODS: Long-term indomethacin therapy was defined as indomethacin use for at least 48 hours. Log-binomial regression was used to estimate the relative risk of PTB in the LIT group compared with a non-LIT group. Cox regression was used to evaluate the association between LIT use and FLS-to-delivery survival. MAIN OUTCOME MEASURES: Gestational age (GA) at delivery. RESULTS: Among the 411 pregnancies included, a total of 180 patients (43.8%) received LIT after FLS and 231 patients (56.2%) did not. Median GA at fetal intervention did not differ between groups (20.4 weeks). Median GA at delivery was significantly higher in the LIT group (33.6 weeks) compared with the non-LIT group (31.1 weeks; P < 0.001). FLS-to-delivery interval was significantly longer in the LIT group (P < 0.001). The risks of PTB before 34, 32, 28 and 26 weeks of gestation were all significantly lower in the LIT group compared with the non-LIT group (relative risks 0.69, 0.51, 0.37 and 0.18, respectively). The number needed to treat with LIT to prevent one PTB before 32 weeks of gestation was four, and to prevent one PTB before 34 weeks was five. CONCLUSION: Long-term indomethacin after FLS for TTTS was found to be associated with prolongation of pregnancy and reduced risk for PTB. TWEETABLE ABSTRACT: Long-term indomethacin used after fetoscopic laser surgery for twin-to-twin transfusion syndrome is effective in prolonging pregnancy and reducing the risk for preterm birth; especially extreme preterm birth.

Monochorionic diamniotic twin pregnancies.

About 1 in 5 twin pregnancies are monochorionic diamniotic. In these twins, transfusion imbalances may develop because of the vascular anastomoses that are invariably present. The most severe imbalance is twin-twin transfusion syndrome, which presents as a significant amniotic fluid difference diagnosed on ultrasound scan, usually before 26 weeks. Another transfusion imbalance is twin anemia polycythemia sequence, which is a severe hemoglobin difference occurring mainly after 26 weeks in previously uncomplicated pregnancies. Fetoscopic laser coagulation of the anastomoses addresses the cause of these transfusion imbalances. Beside transfusion imbalances, the monochorionic placenta may be unevenly divided, or one part may be dysfunctional, leading to an intertwin growth difference of more than 20%. Here, laser ablation of the anastomoses will usually not cure the problem, but it aims to protect the appropriately growing twin if the growth-restricted cotwin dies. In monochorionic twins, structural anomalies are twice as common as in singleton pregnancies, probably because of a teratogenic effect of the embryonic splitting or because of transfusion imbalances. In contrast, chromosomal anomalies seem less common, possibly because they more likely result in an early demise. Selective reduction is feasible in monochorionic pregnancies but carries increased risks of loss, miscarriage, and early birth than selective reduction in a dichorionic setting. Finally, if one monochorionic twin dies spontaneously, its cotwin may acutely exsanguinate into the demised cotwin, which may result in the loss of both twins or brain damage in the surviving twin. This update addresses the pathophysiology, diagnosis, and management of these common complications in monochorionic diamniotic twin pregnancies.

Evaluation of the new expert consensus-based definition of selective fetal growth restriction in monochorionic pregnancies.

OBJECTIVE: To compare the outcomes of a cohort of monochorionic pregnancies with selective fetal growth restriction (sFGR) diagnosed according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) definition published in 2015 with a cohort considered as sFGR according to new expert consensus-based diagnostic parameters published in 2019. METHODS: This was a retrospective study, conducted between January 1st 2010 and July 30th 2019. We reviewed the medical records of all the monochorionic pregnancies followed in our center including perinatal outcomes. Pregnancies complicated by fetal anomalies, infection, twin-twin transfusion syndrome, twin anaemia-polycythemia sequence and twin reversed arterial perfusion sequence were excluded. Patients were grouped according to the 2015 ISUOG definition into: normal (Group 1), sFGR (Group 2), and monochorionic pregnancies with abnormal growth that did not fulfill the full criteria for sFGR (Group 3). After the initial classifications were made, an additional group, was created, including all pregnancies reclassified as sFGR according to the 2019 expert consensus parameters (Group 4). RESULTS: During the study period, 291 monochorionic pregnancies were followed in our center, 132 of whom were eligible for inclusion in the final analysis. The prevalence of sFGR increased from 17.4% to 26.5% after applying the expert consensus-based parameters to the study population. Compared to group 1, group 2 had higher rates of emergency cesarean, neonatal intensive care admissions, invasive and noninvasive ventilation, surfactant use, metabolic disorders and lower gestational ages at birth. In contrast, the neonatal outcomes of Groups 1 and 4 were not significantly different. CONCLUSION: When the 2019 consensus-based diagnostic parameters for sFGR were applied to our study population, the number of sFGR cases increased by over 50%, without any improvements in perinatal outcomes. Larger prospective studies are needed to examine the potential clinical implications of these new parameters for sFGR in monochorionic pregnancies.

Síndrome de transfusão feto-fetal: revisão de literatura / Twin-twin transfusion syndrome: a literature review

A síndrome de transfusão feto-fetal é uma complicação das gestações gemelares monocoriônicas. Além de ocorrer comumente no segundo trimestre, apresenta elevada morbimortalidade fetal e neonatal, e taxas de incidência que variam de 10 a 15% dentre todas as gravidezes monocoriônicas. O objetivo deste estudo é realizar uma revisão de literatura a partir de levantamento bibliográfico acerca dos principais aspectos epidemiológicos, clínicos e terapêuticos da STFF. A base de dados PubMed foi consultada, uma vez que os termos de pesquisa utilizados foram "síndrome de transfusão feto-fetal", "diagnóstico" e "tratamento". Obtiveram-se sessenta e oito artigos de revisão de literatura e/ou revisão sistemática, sendo que apenas vinte e nove foram selecionados após aplicação dos critérios de elegibilidade. Em relação à fisiopatologia, a síndrome é explicada pela transferência sanguínea direta entre os fetos gemelares através de anastomoses arteriovenosas placentárias, conceitualmente determinando a existência de um feto receptor e outro doador. Embora as gestantes comumente se apresentam assintomáticas, as repercussões clínicas fetais costumam ser graves. O diagnóstico é exclusivamente ultrassonográfico e deve ser feito o mais precocemente possível, ressaltando-se a importância da detecção da corionicidade da gestação gemelar, além de acompanhamento ultrassonográfico seriado para rastreio do desenvolvimento da síndrome. Apesar de ainda não haver protocolo de tratamento bem estabelecido, a ablação dos vasos placentários a laser é tida como o padrão-ouro dentre as opções terapêuticas disponíveis. Apresenta elevada taxa de sobrevida de pelo menos um dos fetos e baixos índices de sequelas neurológicas neonatais, podendo ser realizada somente até a 26ª semana de gestação.

Twin-twin transfusion syndrome is a complication of monochorionic twin pregnancies. In addition to commonly occurring in the second trimester, it has high fetal and neonatal morbidity and mortality and incidence rates ranging from 10 to 15% among all monochorionic pregnancies. This study aims to perform a literature review based on a bibliographic survey about the main epidemiological, clinical and therapeutic aspects of TTTS. The PubMed database was consulted, as the search terms used were "twin-twin transfusion syndrome", "diagnosis", and "treatment". Sixty-eight literature review and systematic review articles were obtained, and only twenty-nine were selected after applying the eligibility criteria. About the pathophysiology, the syndrome is explained by direct blood transfer between the twin fetuses through placental arteriovenous anastomoses, determining the existence of a recipient fetus and another donor. Although pregnant women are usually asymptomatic, the clinical fetal repercussions are often severe. Diagnosis is exclusively ultrasonographic and must be made as early as possible, emphasizing the importance of detecting chorionicity in twin pregnancy, in addition to serial ultrasonographic follow-up to track the development of the syndrome. Although there is still no well-established treatment protocol, endoscopic laser ablation of vascular anastomoses is considered the gold standard among the available therapeutic options. It has a high survival rate for at least one of the fetuses and low rates of neonatal neurological sequelae and can only be performed until the 26th week of pregnancy.

Long-term neurodevelopmental outcomes of the pump twin in twin reversed arterial perfusion sequence treated by radiofrequency ablation.

OBJECTIVES: To assess long-term neurodevelopmental outcomes in children after radiofrequency ablation (RFA) for twin reversed arterial perfusion (TRAP) sequence. METHODS: This cross-sectional study included children who underwent RFA for the TRAP sequence between 2012 and 2018. We assessed neurodevelopment in children using the Kinder Infant Development Scale, a validated questionnaire. The developmental quotient (DQ) assessed in nine subscales was calculated as the developmental age divided by the chronological age. Neurodevelopmental delay (NDD) was defined as a DQ of <70 points. RESULTS: In total, 38 children from 37 pregnancies underwent RFA for the TRAP sequence during the study period; 6 fetuses died in utero. We sent the questionnaire to the parents of the 32 surviving children and obtained answers for 27 (84%). The median age at the assessment was 2 years and 5 months old. The median total DQ was 111 (80-150). Most median DQs in the nine subscales were above 70. The incidence of NDD was 0% (0/27). There were no marked differences in DQ by chorionicity. CONCLUSIONS: Children who survived after RFA for TRAP sequence showed favorable long-term neurodevelopmental outcomes. Radiofrequency ablation seems to rarely affect fetal neurodevelopment. Pregnant women with TRAP sequence are encouraged to be treated by RFA.

Placental Abruption after Fetoscopic Laser Surgery in Twin-Twin Transfusion Syndrome: The Role of the Solomon Technique.

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) is a complication in monochorionic twin pregnancies which is preferably treated with fetoscopic laser surgery. A few small studies suggested a possible association between the Solomon laser technique and placental abruption. METHODS: The objective of this study is to compare the rate of and to explore potential risk factors for placental abruption in TTTS treated with fetoscopic laser surgery according to the Selective and Solomon laser technique. We conducted a large retrospective cohort study of consecutive TTTS-cases treated with fetoscopic laser surgery in Shanghai, China, and Leiden, The Netherlands treated with either the Selective laser technique (Selective group) or Solomon laser technique (Solomon group). RESULTS: The rate of placental abruption in the Selective group versus the Solomon group was 1.7% (5/289) and 3.4% (15/441), respectively (p = 0.184). No risk factors for placental abruption were identified. Placental abruption was associated with lower gestational age at birth (p = 0.003) and severe cerebral injury (p = 0.003). CONCLUSION: The prevalence of placental abruption in TTTS after fetoscopic laser surgery is low, although it appears higher than in the overall population. Placental abruption is associated with a lower gestational age at birth, which is associated with severe cerebral injury. The rate of placental abruption was not significantly increased with the use of the Solomon technique. Continued research of placental abruption in TTTS is necessary to determine why the rate is higher than in the overall population.

Predicting Adverse Outcomes in Monochorionic-Diamniotic Twins: The Role of Intertwin Discrepancy in Middle Cerebral Artery Doppler Measurements and the Cerebroplacental Ratio.

OBJECTIVE: This study was aimed to evaluate the role of intertwin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) and cerebroplacental ratio (CPR) for the prediction of adverse outcomes in monochorionic-diamniotic (MCDA) twin pregnancies. STUDY DESIGN: A retrospective cohort study of MCDA pregnancies that underwent ultrasound surveillance at a perinatal referral center from 2007 to 2017. Intertwin MCA-PSV discrepancy (MCA-ΔPSV-MoM) was defined as the absolute difference of MCA-PSV multiple of the median (MoM) for gestational age between twins. Intertwin CPR discrepancy (CPR-Δ) was defined as the absolute difference of CPR between twins. The maximum MCA-ΔPSV-MoM and CPR-Δ before and after 26 weeks of gestation were assessed as predictors of pregnancy and neonatal outcomes through simple logistic regression models and Pearson's correlation coefficients. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of maximum MCA-ΔPSV-MoM and CPR-Δ. RESULTS: A total of 143 MCDA pregnancies met inclusion criteria. There was a significant association between MCA-ΔPSV-MoM at <26 weeks and the development of twin anemia-polycythemia sequence (TAPS; p = 0.007), intrauterine fetal demise (IUFD; p = 0.009), and neonatal intensive care unit (NICU) admission (p < 0.05). MCA-ΔPSV-MoM at ≥26 weeks was associated with the development of TAPS (p < 0.001). CPR-Δ at <26 weeks was associated with the development of twin-twin transfusion syndrome (TTTS; p = 0.03) and NICU admission (p = 0.02). MCA-ΔPSV-MoM at ≥26 weeks was highly predictive of TAPS (area under curve [AUC] = 0.92). A cut-off of 0.44 would identify TAPS with 100% sensitivity and 73% specificity. CONCLUSION: In MCDA pregnancies, intertwin MCA and CPR discrepancies are associated with adverse pregnancy and neonatal outcomes, including TAPS, TTTS, IUFD, and NICU admission. Evaluation of intertwin MCA and CPR differences demonstrated the potential for clinical predictive utility in the surveillance of MCDA twin pregnancies. KEY POINTS: · Intertwin discrepancy of MCA-PSV and CPR is associated with adverse pregnancy outcomes.. · Intertwin differences in Doppler ultrasound may occur prior to meeting diagnostic criteria for TTTS or TAPS.. · There is potential clinical predictive utility in MCA and CPR surveillance of MCDA twin pregnancies..

Risk Factors Associated with Preterm Prelabor Rupture of Membranes after Cord Occlusion in Monochorionic Diamniotic Twins.

INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) is a common complication after fetal surgeries. The aim of this study was to assess risk factors for and outcomes after PPROM following cord occlusion (CO) in monochorionic diamniotic (MCDA) pregnancies. METHODS: This was a retrospective cohort study of 188 consecutive MCDA pregnancies treated by bipolar or laser CO, either primarily because of discordant malformation (dMF) or severe selective fetal growth restriction (sFGR), or secondarily when complete bichorionization was not possible in case of twin-to-twin transfusion syndrome (TTTS) or sFGR. Intentional septostomy was performed when needed. The procedure-related PPROM was defined as rupture of membranes <32 weeks' gestation (PROM <32 weeks). Selected pre-, intra-, and early postoperative variables were analyzed by univariate and binomial logistic regression to determine they are correlated to PROM <32 weeks after CO. RESULTS: Between 2006 and 2017, 188 cases underwent CO. Diagnosis was TTTS in 28.2% (n = 53), severe sFGR in 49.5% (n = 93), and dMF in 22.3% (n = 42). PROM <32 weeks occurred in 21.3% (n = 40), resulting in worse perinatal outcomes, as preterm birth <32 weeks occurred in 80.7% (vs. 8.3%, p = 0.000), procedure-to-delivery interval was 47.5 days (vs. 125, p = 0.000), gestational age (GA) at birth 30.0 weeks (vs. 37.7 weeks, p = 0.000), and survival 65.0% (vs. 91.1%, p = 0.000). In univariate analysis, indication, anterior placenta, cervical length, GA at surgery, operation time, amniodistention and drainage fluid volumes, chorioamniotic membrane separation, and septostomy were selected as relevant factors to be included in the regression model. In a multivariate analysis, TTTS was the only factor associated to PROM <32 weeks (OR 3.5 CI 95% 1.5-7.9). CONCLUSIONS: PROM <32 weeks after CO increases the risk of preterm delivery. In this cohort, the membrane rupture was more likely when CO was done in the context of TTTS.

Fetal Growth in Multiple Gestations: Evaluation and Management.

Multifetal gestation pregnancies present a clinical challenge due to unique complications including growth issues, prematurity, maternal risk, and pathologic processes, such as selective intrauterine growth restriction (sIUGR), twin-to-twin transfusion syndrome (TTTS), and twin anemia-polycythemia sequence. If sIUGR is found, then management may involve some combination of increased surveillance, fetal procedures, and/or delivery. The combination of sIUGR with TTTS or other comorbidities increases the risk of pregnancy complications. Multifetal pregnancy reduction is an option when a problem is confined to a single fetus or when weighing the risks and benefits of a multifetal gestation in comparison to a singleton pregnancy.

The mystery of monozygotic twinning II: What can monozygotic twinning tell us about Amyoplasia from a review of the various mechanisms and types of monozygotic twinning?

Monozygotic (MZ) twins ("identical twins") are essentially unique to human beings. Why and how they arise is not known. This article reviews the possible different types of MZ twinning recognized in the previous article on twins and arthrogryposis. There appear to be at least three subgroups of MZ twinning: spontaneous, familial, and those related to artificial reproductive technologies. Each is likely to have different etiologies and different secondary findings. Spontaneous MZ twinning may relate to "overripe ova." Amyoplasia, a specific nongenetic form of arthrogryposis, appears to occur in spontaneous MZ twinning and may be related to twin-twin transfusion.