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Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery
Abstract
This study was undertaken to determine the long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome treated with laser.
All twin-to-twin transfusion syndrome cases treated at our center with laser between August 2000 and December 2003 were included in the study. Neurologic, mental, and psychomotor development at 2 years of age corrected for prematurity was assessed in all twin-to-twin transfusion syndrome survivors. Neurodevelopmental impairment was defined as any of the following: cerebral palsy, deafness, blindness, mental, or psychomotor development index of the Bayley Scales of Infant Development II less than 2 SD.
A total of 82 twin-to-twin transfusion syndrome pregnancies were treated with fetoscopic laser surgery during the study period. Perinatal survival was 70% (115/164). The incidence of neurodevelopmental impairment was 17% (19/115) and was due to cerebral palsy (n = 8), mental developmental delay (n = 9), psychomotor developmental delay (n = 12), and deafness (n = 1).
The incidence of neurodevelopmental impairment in twin-to-twin transfusion syndrome survivors treated with laser is high and warrants long-term follow-up.
... d espite the success of fetoscopic laser surgery (FLS) for the treatment of severe twin-twin transfusion (TTTS), preterm delivery with or without preterm premature rupture of membranes (PPROM) remains a major complication (1)(2)(3)(4). The average gestational age at delivery after procedure ranges between 29 to 33 wk (1,5). ...
... The average gestational age at delivery after procedure ranges between 29 to 33 wk (1,5). Aside from the cost of caring for the premature infants, preterm delivery is directly associated with long-term neurological deficits in TTTS (4,6), undermining the complete benefits of such intervention. PPROM which affects 20-32% of cases is the most important risk factor leading to preterm delivery (2,(7)(8)(9)(10). ...
Preterm premature rupture of membranes remains a major complication after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). We studied the histologic changes of fetal membranes post-FLS and investigated a possible impact of amniotic fluid (AF) dilution.
Fetal membranes of 31 pregnancies that underwent FLS for TTTS were investigated histologically at delivery at different sites: trocar site of recipient sac and at distance, donor sac and inter-twin membrane.
The trocar insertion site on the recipient sac showed no signs of histologic hallmarks of healing. Wide-spread alteration in collagen organization and higher apoptotic index in the amnion of the recipient sac which were absent in donor's and reference membranes. To explain the mechanisms, we analyzed the AF composition of recipient sacs from TTTS pregnancies versus GA-matched healthy singleton controls and found glucose, protein and lactate dehydrogenase activity were all significantly lower in TTTS sacs consistent with over-dilution of recipient's AF (~2 fold). In-vitro exposure of healthy amniochorion to analogous dilutional stress conditions recapitulated the histologic changes and induced apoptosis and autophagy.
Alteration in structural integrity of the recipient's amniochorion, possibly in response to dilution stress, along with ineffective repair mechanisms may explain the increased incidence of preterm birth post-FLS.Pediatric Research (2015); doi:10.1038/pr.2015.105.
... 3 It is well known that fetoscopic selective laser ablation of placental vascular anastomoses (FPL) as treatment for TTTS and umbilical cord occlusion (UCO) of the twin at high risk of death (severe cases of s-IUGR or discordant congenital defect) have a protective role in terms of co-twin survival and cerebral injury in the survivor co-twin. 4 However, these procedures do not ensure definitively the absence of these complications. 5 Parent counseling and clinical management are challenging in MC twins with s-IUFD, and there is great controversy relating to the follow-up they need (frequency of ultrasound scans [US], neuroimaging including neurosonography and/or magnetic resonance imaging [MRI]). ...
Introduction
The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury.
Material and methods
Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012–2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development.
Results
A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty‐five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy‐group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04–1.41, p = 0.014) and was higher in those surviving co‐twins who developed anemia (OR 9.27, 95% CI: 1.50–57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68–11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome.
Conclusions
Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co‐twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.
... Moreover, long term visual outcomes of ROP were lacking. Studies focusing on long-term follow-up in TTTS twins have shown that the incidence of blindness (bilateral) does not differ between donors and recipients [38][39][40][41][42]. However, this may be due to early intervention and successful ROP screening. ...
Introduction:
The purpose of this study was to evaluate the within-pair difference in retinopathy of prematurity (ROP) between donors and recipients with twin-to-twin transfusion syndrome (TTTS) and to identify risk factors for ROP development.
Methods:
This retrospective cohort study included 147 TTTS twin pairs managed between 2002-2022 and eligible for ROP screening. Primary outcomes were any stage ROP and severe ROP. Secondary outcomes were hemoglobin at birth, red blood cell transfusions, mechanical ventilation days, postnatal steroids and neonatal morbidity.
Results:
Rates of any stage ROP (23% vs. 14%) and severe ROP (8% vs. 3%) were significantly higher in donors compared to recipients. Donors received a higher number of blood transfusions (1 (±1.9) vs. 0.7 (±1.5)). Five factors were univariately associated with any stage ROP: donor status (OR 1.9; 95% CI 1.3-2.9), lower GA at birth (OR 1.7; 95% CI 1.4-2.1), small for GA (OR 2.1; 95% CI 1.3-3.5), mechanical ventilation days (OR 1.1; 95% CI 1.1-1.2) and blood transfusions in phase 1 (OR 2.3; 95% CI 1.2-4.3). Three factors were independently associated with any stage ROP: donor status (OR 1.8; 95% CI 1.1-2.9), lower GA at birth (OR 1.6; 95% CI 1.2-2.1) and mechanical ventilation days (OR 1.1, 95% CI 1.0-1.1). Donor status was univariately associated with severe ROP (OR 2.3, 95% CI 1.1-5.0).
Conclusion:
Any stage ROP and severe ROP are detected twice as frequently in donors compared to recipients. Increased awareness for ROP is needed in donors, especially those with lower GA at birth and longer duration of mechanical ventilation.
... Research on long-term neurodevelopmental outcomes found that the survivors of TTTS often have neurodevelopmental injury. Both recipients and donors are equally at risk for adverse neurodevelopmental outcomes [25]. In this study, we investigated the hub methylation genes using methylation microarray to explore the pathogenesis of neurological impairment in TTTS. ...
Background: DNA methylation (DNAm), is an important transcriptional regulation mechanism, relevant to various diseases. Twin-to-twin transfusion syndrome (TTTS) is a complication in twin pregnancies resulting from disproportionate blood circulation. Survivors of TTTS show a high risk of neurodevelopmental abnormalities, particularly in the hippocampus, which is important in learning and memory. Here, we investigate gene expression and DNAm in hippocampus tissues of TTTS specimens.
Methods: DNAm and gene expression levels were compared among the three groups: 10 recipients, 10 donors, and 10 matched control, using methylation microarray. We further explored the immune infiltration of six immune cell sub-populations using EpiDISH analysis. The methylated sites related to immune cell infiltration were identified using the WGCNA package. We explored the core methylation genes in the protein-protein interaction network using the MCODE plugin in Cytoscape software.
Results: There were 188 differential methylation sites among three groups. Based on WGCNA, we found that the turquoise module containing 174 CpG sites is significantly related to the immune infiltration level. And four hub genes correlated with immune infiltration level, namely, PTPRJ, FYN, LYN, and AKT1, and were identified using gene sub-network analysis.
Conclusions: We identify the four hub methylation genes related to immune infiltration in the TTTS. The molecular function of hub genes is still explored in the future research.
... Sin embargo, la detección de lesiones cerebrales depende del intervalo lesión-diagnóstico. A diferencia de las lesiones hemorrágicas, las lesiones isquémicas en la fase temprana pueden ser difíciles de visualizar (22)(23)(24)(25) . La exploración inicial normal no descarta lesiones y la evidencia de anomalías ...
Los embarazos múltiples, la mayoría de los cuales son gemelares, tienen un riesgo sustancialmente mayor de morbimortalidad fetal comparado con los embarazos únicos. La muerte fetal de uno de los gemelos en embarazos gemelares monocoriónicos es más frecuente que en embarazos gemelares dicoriónicos. La muerte fetal intrauterina ocurre en 1 a 7% de todos los embarazos gemelares y aumenta considerablemente la tasa de complicaciones del gemelo superviviente, incluyendo pérdida fetal, parto prematuro y daño de órgano final. La edad gestacional en que ocurre la muerte fetal intrauterina y la corionicidad de los embarazos múltiples son los dos factores más importantes al considerar los riesgos del gemelo superviviente. La morbimortalidad de estos embarazos puede disminuir con la identificación del embarazo de riesgo y la vigilancia prenatal intensiva. Los embarazos monocoriónicos son más difíciles de manejar y a menudo los embarazos se interrumpen entre las 34 y 36 semanas. Los embarazos dicoriónicos se pueden interrumpir más cerca del término.
... The superiority of laser coagulation therapy over serial amnioreduction regarding survival rates has subsequently been demonstrated in a population-based trial and a randomized controlled trial (RCT) 3,4 . Furthermore, laser therapy of TTTS leads to an improvement in long-term neurodevelopmental outcome [5][6][7][8] . However, laser therapy may lead to complications such as iatrogenic preterm prelabor rupture of membranes 9 , twin anemia-polycythemia sequence (TAPS) 10 , reversal or recurrence of TTTS 11 and intrauterine fetal death. ...
Objective:
To investigate the growing experience and learning curve of fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin-twin transfusion syndrome (TTTS) and its influence on perinatal outcome in a single-center setting.
Methods:
Between January 1995 and March 2013 we performed laser therapy in 1020 consecutive pregnancies with TTTS between 15.1 and 27.4 weeks' gestation. We compared perinatal outcome in blocks of five sequential groups of 200 cases, taking into account several covariates in order to adjust for case mix and to demonstrate learning curves and success rates.
Results:
The percentage of pregnancies with survival of both fetuses increased from 50.0% (n = 100) in the first 200 cases to 69.5% (n = 153) in the last 220 cases (P = 0.018 for trend) and the overall survival rate for both fetuses in the complete series of 1019 cases with known outcome was 63.3% (n = 645). The survival rate of at least one fetus increased from 80.5% (161/200) in the first group to 91.8% (202/220) in the last group (P = 0.072 for trend) and the overall survival rate of at least one fetus in the complete series was 86.7% (883/1019). In the total population, the mean gestational age at delivery of pregnancies with at least one liveborn neonate was 33.7 ± 3.2 weeks, with a mean interval of 12.9 ± 4.0 weeks between intervention and delivery. Among the first two groups, 124 pregnancies had anterior placentae and were treated with a 0° fetoscope. These cases had the poorest overall outcome, with a double-twin survival rate of 44.4% (55/124), which increased to 65.1% (207/318; P = 0.001) after the introduction of a 30° fetoscope for cases with anterior placenta. The success rate for double-twin survival reached a plateau of 69% at 600 procedures, a rate equalled by a new operator who was trained hands-on and performed 174 of the last 400 procedures.
Conclusions:
We report the largest single-center experience of laser coagulation in TTTS. We observed a continuous increase in double-twin survival rate owing to the growing experience based on the learning curve and refinements in fetoscopic instruments and techniques. These data provide strong arguments for the centralization of minimally invasive intrauterine surgery in specialized high-volume centers. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
... Survivors of intrauterine co-twin death (CD) have a greater than 20% average risk of NDI. [1][2][3] Although fetoscopic laser photocoagulation of placental anastomosing vessels (FLPAV) is now the treatment of choice for sonographically diagnosed TTTS of Quintero stage II or greater, 4 between 3% and 16% of survivors have brain abnormalities that are demonstrable on post-natal cranial ultrasonography [5][6][7] and 6% to 25% suffer from NDI. [8][9][10][11][12] In a recent evaluation of children participating in the Eurofoetus trial, 12% of survivors of TTTS treated with FLPAV were found to have neurological morbidity, either owing to prematurity or as a result of haemodynamic changes associated with the disease and its treatment. 13 However, survivors of CD have an even higher risk of NDI especially when the demise occurs prior to or without FLPAV treatment for TTTS. 1 An uncertain proportion of the total cerebral injuries that occur in complicated monochorionic gestations (cMCGs) are prenatal, and identification of such injuries has the potential to change pregnancy counselling and management. ...
Objective:
To determine the additional diagnostic information provided by prenatal (fetal) magnetic resonance imaging (pMRI) following tertiary ultrasound (US) for fetal cranial abnormalities in complicated monochorionic gestations (cMCGs) METHODS: Women with cMCGs complicated by twin - twin transfusion syndrome (TTTS), co-twin demise (CD), selective intrauterine growth restriction (sIUGR), and / or twin anemia - polycythemia sequence (TAPS) who were referred for pMRI after tertiary US were included.
Primary outcome:
additional diagnostic information by pMRI that changed prognostic counselling.
Results:
33 women with 48 live fetuses had pMRI at a median of 25 weeks (range: 21 - 29). 3/10 survivors of spontaneous CD, 1/8 survivors of CD after TTTS and 1/30 co-survivors had diagnostic information added by pMRI that altered counselling; US was normal in 2 and in the other 3 under- represented parenchymal injury (5/33 = 15%; 95% CI +/- 0.27 - 0.03). Additional findings included occipital lobe infarction, hemispheric injury, dural sinus thrombosis, ischemia producing polymicrogyria, and intraventricular hemorrhage. Another 8 /33 women had additional information provided by pMRI that did not alter counselling.
Conclusion:
pMRI resulted in changed prognostic counselling in 5/33 pregnancies. Evaluation of incorporation of pMRI into routine surveillance of complicated MCGs is needed.
... Documentation of survivors with complications who did not undergo such treatments are not available. Among those children who were tracked and re-evaluated post-surgery, common complications include: cerebral palsy, psycho-motor developmental delay, borderline cognitive development, major neurodevelopmental impairment, motor development issues, blindness and deafness [32][33][34]. Given that fetoscopic selective laser ablation surgery is shown to produce more favorable outcomes, children who received no treatments may fair worse, however no known evidence exists. ...
Background:
Twin-to-twin transfusion syndrome (TTTS) affects 10-20 % of monochorionic diamniotic (MCDA) births and accounts for 50 % of fetal loss in MCDA pregnancies. This exploratory qualitative study identified shared experiences, including potential emotional and psychosocial impacts, of this serious disease.
Methods:
Forty-five publicly accessible, online stories posted by families who experienced TTTS were analyzed using grounded theory.
Results:
Shared TTTS experiences included a common trajectory: early pregnancy experiences, diagnostic experiences, making decisions, interventions and variable outcomes. Families vacillated between emotional highs such as joy, excitement and relief, and lows including depression, anxiety, anger and grief.
Conclusions:
TTTS disease experience can be considered an "emotional roller coaster" exacerbated by TTTS's unpredictable and quickly changing nature with the potential for emotional and psychosocial effects. Increased TTTS awareness and research about its corresponding impacts can ensure appropriate patient and family support at all phases of the TTTS experience.
... McIntosh et al. (2014) investigated the long-term neurodevelopmental outcome of a cohort of 3-to 5-year-old (Lopriore et al., 2007;van Klink et al., 2014) in TTTS after laser are not included in this table because the included children are more fully described in the multi-center follow-up of this studies (Lopriore et al., 2009;van Klink et al., 2015b). CP = cerebral palsy; NDI = neuro developmental impairment defined as CP, severe cognitive and/or motor delay (<2 SD), blindness and/ or deafness; NND = neonatal death; GP = general practitioner; GA = gestational age. ...
Twin–twin transfusion syndrome (TTTS) is a severe complication of monochorionic (MC) twin pregnancies associated with high perinatal mortality and morbidity rates. Management in TTTS is a major challenge for obstetricians and neonatologists. Twins with TTTS are often born prematurely after an extremely distressing and highly hazardous fetal period. Follow-up studies report varying rates of cerebral palsy (CP) and long-term neurodevelopmental impairment (NDI). This review discusses the latest findings on the long-term outcome of TTTS survivors, possible risk factors for long-term impairment, and provides recommendations for future research.
... A recent randomised control trial has also shown that fetoscopic laser surgery (FLS) has more favourable survival rates and a significantly reduced risk of neurodevelopmental impairment when compared to amnioreduction 11 . Despite these advances and improved outcomes, significant rates of fetal demise and neurological impairment such as cognitive and motor developmental delay remain [12][13][14] . ...
Untreated twin-twin transfusion syndrome (TTTS) is associated with significant mortality and neurological impairment. Fetoscopic laser surgery (FLS) is the treatment of choice. We sought to assess intracranial abnormalities in TTTS twins following treatment. In this prospective, blinded study MRI scans were performed on 3 groups; (1) monochorionic diamniotic (MCDA) twins with TTTS who had undergone FLS (n=10), (2) MCDA twins without TTTS (n=8) and (3) dichorionic twins (n=8). Scans were scored as either normal or abnormal. The primary outcome was a composite of abnormal MRI brain or intrauterine fetal demise. The primary outcome occurred in 6/10 (60%) of the TTTS group versus 3/8 (37.5%) in the MCDA group. The primary outcome was significantly different across all study groups [p = 0.029; X† = 7.112]. We found that twins treated for TTTS are more likely to have abnormalities on MRI brain at term than other twin groups. This group merits term-corrected MRI as part of their postnatal assessment.
To cite: Sahu M. Twin studies as an innovative approach to address research questions in cancer care within primary care settings. ABSTRACT This paper proposes the utilisation of twin studies as a novel and powerful methodological approach to investigate critical research questions pertaining to cancer prevention, screening, diagnosis, treatment and survivorship within primary care contexts. The inherent genetic similarity between monozygotic (MZ) (identical) twins provides a unique opportunity to disentangle genetic and environmental influences on cancer-related outcomes. MZ twins share virtually identical genetic makeup, offering a unique opportunity to discern the relative contributions of genetic and environmental factors to cancer-related outcomes. In contrast, dizygotic (DZ) twins, also known as fraternal twins, develop from two separate eggs fertilised by two different sperm and share on average 50% of their genetic material, the same level of genetic similarity found in non-twin siblings. Comparisons between MZ and DZ twins enable researchers to disentangle hereditary factors from shared environmental influences. This methodology has the potential to advance our understanding of the multifaceted interplay between genetic predisposition, lifestyle factors and healthcare interventions in the context of cancer care. This paper outlines the rationale, design considerations and potential applications of twin studies in primary care-based cancer research
Monochorionic twin pregnancies have an increased risk for morbidity and mortality. Due to advancements in screening and treatment strategies, mortality rates have decreased. Improving survival rates demand a shift in scope towards long-term outcomes. In this review we focus on neurodevelopmental outcome in survivors from complicated monochorionic twin pregnancies, including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), acute peripartum TTTS, acute perimortem TTTS, selective fetal growth restriction (sFGR) and monoamnionicity. Our aim is to provide an overview of the current knowledge on the long-term outcome in survivors, including psychomotor development and quality of life, and provide recommendations for future research and follow-up programs.
The literature concerning the neurocognitive evolution of children with transfusion-transfusion syndrome (TTS) is poor beyond the first year of life. It is therefore of particular interest to trace the developmental and management pathway, from the age of 18 months to 11 years, of a boy who presented with TTS in utero. This example illustrates the benefit of early multidisciplinary support and the diagnostic issues raised with the development of the child.
Objective:
A recent randomized controlled trial (RCT) demonstrated no difference in 6-month survival in expectantly managed stage I twin-twin transfusion syndrome (TTTS) patients and those undergoing immediate laser surgery. We aimed to describe outcomes following immediate laser surgery at a single fetal surgery center.
Methods:
A retrospective study of monochorionic diamniotic twins diagnosed with stage I TTTS who underwent laser surgery between 16-26 gestational weeks from 2006-2019. The primary outcome was 6-month survivorship. Intact survival was also assessed. Secondarily, outcomes were compared to the RCT expectant management group.
Results:
Of 126 consecutive stage I TTTS patients, 114 (90.5%) met inclusion criteria. Median (range) gestational age at delivery was 34.1 (20.6 - 39.4) weeks. At 6 months, the proportion of patients with at-least-one survivor in the single-center-laser cohort was 97.4%, with 88.6% dual survivorship. Neurological morbidity outcomes were available in 110 pregnancies (220 fetuses). Severe neurological morbidity occurred in 2.7% (6/220), and 6-month survival without severe neurological morbidity was 90.0%. Outcomes compared favorably with the RCT expectant management group.
Conclusions:
Given favorable survival and neurological outcomes, laser surgery is a reasonable treatment option for stage I TTTS at experienced fetal surgery centers. Further study is warranted to optimize treatment strategies. This article is protected by copyright. All rights reserved.
This chapter gives an update on the current level of knowledge of the neurological and long-term neurodevelopmental outcome in complicated monochorionic twin pregnancy, including twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, twin reversed arterial perfusion, severe discordant anomalies, and single fetal demise. Risk factors for adverse long-term outcome are highlighted and future research- and care suggestions are provided.
Objectives:
To evaluate the association of intertwin differences in umbilical artery pulsatility index (DUAPI) and infant survival in twin-to-twin transfusion syndrome (TTTS).
Methods:
Absolute DUAPI was calculated prior to laser surgery. Receiver-operating characteristics (ROC) curve analysis provided an intertwin DUAPI cutoff of 0.4 for the prediction of double twin survival to 30 days of life. Infant survival was compared between women with an intertwin DUAPI <0.4 and ≥0.4 in the whole cohort, in TTTS cases with Quintero stages I/II and in those with Quintero stages III/IV. Regression analyses were performed to evaluate the association of intertwin DUAPI <0.4 and infant survival adjusted for confounders.
Results:
In total, 349 TTTS cases were included. Double twin survival to 30 days was observed in 67% (234/349) of cases. Significant differences in double twin survival was seen between intertwin DUAPI groups in the whole cohort (76.8 vs. 52.2%; p<0.001), in women with TTTS Quintero stage I or II (77.8 vs. 58.5%; p=0.015) as well as in women with TTTS Quintero stage III or IV (75 vs. 49.5%; p=0.001). Intertwin DUAPI <0.4 conferred a threefold increased chance for double twin survival.
Conclusions:
Small intertwin DUAPI is associated with increased double infant survival in early and advanced TTTS stages.
Monochorionic twin gestations possess disproportionately higher risk for perinatal morbidity and mortality when compared with dichorionic twin pregnancies due to their potential to develop specific complications attributable to a shared placenta and intertwin placental circulation. Since the advent of fetoscopic laser surgery, outcomes of pregnancies affected by twin-twin transfusion syndrome (TTTS) have improved, with reduced rates of mortality and morbidity when compared with amnioreduction or expectant management. The focus of this article is to review the literature regarding neurologic outcomes among pediatric survivors of fetal intervention for TTTS.
Background:
Data on neurodevelopmental outcomes of children surviving after fetoscopic laser surgery (FLS) for twin-to-twin transfusion syndrome (TTTS) are scarce.
Methods:
We retrospectively investigated children children surviving after FLS for TTTS at 16-26 weeks' gestation between 2003-2014. Children were evaluated by standardized neurologic examinations using the Kyoto Scale 2001 at a corrected age of 3 years ±6 months. Neurodevelopmental impairment (NDI) was defined as cerebral palsy (CP), bilateral blindness, bilateral deafness or a developmental quotient (DQ) < 70 points. Brain magnetic resonance imaging (MRI) was performed at term-equivalent age.
Results:
A total of 188 children from 110 twin pregnancies were evaluated. NDI was detected in 16/188 (8.5%) children, including 6 cases of CP (3.2%). No children had bilateral blindness or deafness. An earlier gestational age at delivery was associated with a higher incidence of NDI (P < 0.001). Abnormal brain MRI findings were detected in 9/16 (56%) of children with NDI, including 6/6 (100%) with CP.
Conclusion:
The incidence of NDI in children following FLS at 3 years old was 8.5%. Prematurity is a strong risk factor for NDI. Brain MRI may predict the development of CP. This article is protected by copyright. All rights reserved.
The pathophysiology of twin-to-twin transfusion syndrome (TTTS) is complex, and its understanding has evolved along with the evolution and revolution of fetal diagnostic and therapeutic techniques. Over the last few decades, several therapeutic interventions have been researched for improving the outcomes in TTTS. We present a summary of the current protocols for surveillance, diagnosis, and staging of TTTS in monochorionic pregnancies. We also describe in detail the technique for treatment of TTTS by endoscopic laser photocoagulation.
Die erhöhte Rate von Mehrlingen nach assistierter Reproduktion stellt unverändert ein hohes Risiko für diese Schwangerschaften dar. Sie gelten als Risikoschwangerschaften und bedürfen besonderer Aufmerksamkeit bei der Planung und Durchführung der erforderlichen Überwachungsmaßnahmen, der pränatalen Untersuchungen und Maßnahmen in der Schwangerschaft, bei der Geburt und in der nachgeburtlichen Phase. National und international wird durch Anpassung und Optimierung der Methoden der assistierten Reproduktion versucht, die Mehrlingsrate bei unverändert hohen Schwangerschaftsraten zu senken. Insbesondere im Ausland wird dazu eine Reduktion der transferierten Embryonen bis hin zum Single-Transfer angestrebt. Die konsequente Umsetzung dieser Methode wird in Deutschland aufgrund rechtlicher Restriktionen erheblich erschwert. Daher ist die Mehrlingsrate höher und die Schwangerschaftsrate niedriger als im benachbarten Ausland.
Objectives:
To determine the relationship between intra-amniotic pressure and cervical length (CL) in patients with twin-twin transfusion syndrome (TTTS) undergoing fetoscopic laser photocoagulation (FLP), and to identify pre- or intraoperative factors associated with increased intra-amniotic pressure in this population.
Methods:
This was a prospective cohort study of patients undergoing FLP for TTTS. Exclusion criteria were triplet or higher-order gestation and prior cervical cerclage, amnioreduction or FLP procedure. CL was assessed using preprocedure transvaginal ultrasound. Intra-amniotic pressure measurements were obtained on initial placement of the trocar into the amniotic cavity, using a direct hydrostatic pressure gauge. The relationship between intra-amniotic pressure and CL was assessed using multivariate linear regression analysis, including relevant preoperative and intraoperative variables.
Results:
In total, 283 pregnancies met the inclusion criteria. Quintero stage of TTTS was I in 33 pregnancies, II in 88, III in 150 and IV in 12. Mean gestational age (GA) at FLP was 20.7 ± 3 weeks. Mean intra-amniotic pressure was 23.1 ± 9 mmHg. On unadjusted linear regression analysis, there was no significant association between intra-amniotic pressure and preoperative CL (P = 0.24) or GA at delivery (P = 0.22). On multivariate analysis, the factors associated significantly with intra-amniotic pressure were: number of prior term deliveries (P = 0.03), recipient maximum vertical pocket (P < 0.0001), Quintero stage IV (P = 0.01) and type of anesthesia (sedation vs general anesthesia; P = 0.01).
Conclusion:
In pregnancies with TTTS, intra-amniotic pressure is not associated with CL or GA at delivery. This novel finding suggests that cervical shortening in this population is not mechanically driven. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Twin-to-twin transfusion syndrome typically occurs in the second trimester in 10–15% of monochorionic twin pregnancies. Vascular anastomoses of monochorionic placentae are the underlying cause of the development of the syndrome. If a blood flow imbalance occurs, one fetus becomes the so-called donor twin and the other the recipient. If untreated, perinatal mortality is 80–90%. Fetoscopic laser coagulation of the vascular anastomoses destroys the cause of the syndrome and leads to dual twin survival rates of around 70% and more than 90% of pregnancies with at least one survivor. However, unequal placental sharing, intrauterine death, and severe prematurity are still limiting factors for further improvement of survival rates and decreases in long-term morbidity. Prematurity and neurodevelopmental impairment affect the donor and recipient twins, whereas cardiovascular failure and obstruction of the right ventricular outflow tract are typical complications of recipients, which can lead to long-term morbidity. In this Review, we summarise the literature on follow-up data for survivors of twin-to-twin-transfusion syndrome after laser therapy, including neurodevelopmental outcomes, cardiovascular outcomes, growth, renal function, and ischaemic events, as well as the potential effects of intrauterine programming on later life.
Background:
Twin-Twin Transfusion syndrome is associated with significant mortality and morbidity. Potential treatments require robust evaluation. The aim of this study was to evaluate outcome reporting across observational studies and randomised controlled trials assessing treatments for twin-twin transfusion syndrome (TTTS).
Methods:
Cochrane Central Register of Controlled Trials, EMBASE and Medline were searched from inception to August 2016. Observational studies and randomised controlled trials reporting outcomes following a treatment for TTTS in monochorionic-diamniotic twin pregnancies and monochorionic-triamniotic or dichorionic-triamniotic triplet pregnancies were included. We systematically extracted and categorised outcome reporting.
Results:
Six randomised trials and 94 observational studies, reporting data from 20,071 maternal participants and 3,199 children, were included. Six different treatments were evaluated. Included studies reported sixty-two different outcomes, including 10 fetal, 28 neonatal, 6 early childhood and 18 maternal outcomes. The outcomes were inconsistently reported across trials. For example, when considering offspring mortality, 31 studies (31%) reported live birth, 31 studies (31%) reported intrauterine death, 49 studies (49%) reported neonatal mortality, and 17 studies (17%) reported perinatal mortality. Four studies (4%) reported respiratory distress syndrome. Only 19 (19%) of studies were designed for long-term follow-up and 11 of these studies (11%) reported cerebral palsy.
Conclusions:
Most studies evaluating treatments for TTTS, have often neglected to report clinically important outcomes, especially neonatal morbidity outcomes. Most studies are not designed for long-term follow-up. The development of a core outcome set could help standardised outcome collection and reporting in Twin-Twin Transfusion syndrome studies.
Durch die plazentaren Gefäßanastomosen hängt das Schicksal monochorialer Gemini voneinander ab. Daher hat die Feststellung der Chorion- und Amnionverhältnisse bei der Diagnose einer jeden Mehrlingsgravidität eine fundamentale Bedeutung und sollte bereits in der Frühgravidität, aber spätestens zum Zeitpunkt des Ersttrimesterscreenings erfolgen. Liegt eine monochoriale Plazenta vor, so ist eine engmaschige sonographische Überwachung der Schwangerschaft indiziert. Die monochorialen Zwillinge und ihre spezifischen Komplikationen (schweres Zwillingstransfusionssyndrom [FFTS], selektive Wachstumsrestriktion [sIUGR], Anämie-Polyzythämie-Sequenz [TAPS] im III. Trimester) sowie deren Therapie werden ausführlich dargestellt. Monoamniale Zwillinge sollten ab der 26.–28. SSW engmaschig sonographisch kontrolliert und aufgrund des erhöhten Risikos für einen intrauterinen Tod nach Lungenreifeinduktion ab der 33. SSW per elektiver Sektio entbunden werden. Eine Reduktion von höhergradigen Mehrlingen oder von Drillingen zu Zwillingen ist in Anbetracht der hohen Risiken einer extremen Prämaturität bei abwartendem Verhalten vertretbar und erfolgt bei dichorialen Verhältnissen durch eine intrakardiale Gabe von Kaliumchlorid. Bei monochorialen Verhältnissen kommt nur eine Nabelschnurkoagulation infrage. Eine Reduktion sollte in der 14. SSW erfolgen, und eine adäquate psychologische Evaluation und Betreuung sollte sichergestellt werden.
O objetivo deste estudo foi investigar o desenvolvimento neurológico de gêmeos cujas gestações foram complicadas pela Síndrome de Transfusão Feto-Fetal (STFF) e tratadas pelas técnicas vigentes apresentadas em artigos publicados entre os anos de 2004 e 2014. Trata-se de um estudo retrospectivo, secundário, categorizado como revisão de literatura. A elaboração deste trabalho envolveu cinco etapas: 1. Definição da pergunta; 2. Busca por evidências científicas; 3. Revisão e seleção dos artigos científicos; 4. Análise da
qualidade metodológica dos estudos; 5. Apresentação dos resultados. Na busca na base de dados Web of Science, com a palavrachave fetofetal transfusion, 79 registros corresponderam à consulta. Com os termos combinados fetofetal transfusion and child development foi encontrado um artigo. Na base de dados Pubmed, o termo fetofetal transfusion disponibilizou 1.508 artigos, e com os termos combinados foram identificados seis artigos. Foram avaliados e selecionados 15 estudos que atenderam aos critérios de inclusão. A população estudada representa um grupo de risco para o desenvolvimento neurológico (taxa média de 13,4% de resultados adversos). Dessa forma, o acompanhamento detalhado e cauteloso durante a infância é essencial.
Objectives:
Optimal outcomes after fetoscopic laser surgery (FLS) for twin-twin transfusion (TTTS) depend on the successful completion of ablation of all placental anastomoses. Our objective was to determine the incidence and risk factors for the occurrence of recurrent TTTS (rTTTS) or twin anemia-polycythemia sequence (TAPS) after FLS, and focusing on the impact of different diameters of the cannula.
Methods:
A secondary analysis of prospectively collected data of 666 consecutive patients undergoing laser surgery for TTTS from 2 centers was performed. The main outcomes were rTTTS and post FLS TAPS. Variables including gestational age (GA) at intervention, stage of disease, recipient maximum vertical pocket (MVP), anterior placenta, number of anastomoses, cannula diameter/operative scopes, and use of the Solomon technique. Cannula diameter and the corresponding scopes used were as follows; 8Fr/1.3 mm/0°; 9Fr/2.7 mm/0°; 10Fr/3 mm/0°; 12Fr/3.3-3.7 mm/30°-70° scopes. Cannula diameters were used as surrogates for scopes during analysis. Multivariate logistic regression analysis was performed to identify risk factors associated with rTTTS or TAPS. Each center was considered an independent variable to account for variations in practice. In a nested cohort, placental dye injections were performed on 315 placenta. Multivariate logistic regression was performed to evaluate association.
Results:
rTTTS or TAPS occurred in 61 cases (9%): rTTTS in 8 (1%) and TAPS in 53 (8%). Significant factors after multivariate analysis associated with the complication were cannula diameter (8Fr, 9Fr, 10Fr and 12Fr had rTTTS/TAPS in 24%, 12%, 2% and 0.8%, respectively; p<0.001) and Solomon technique (4.5% with vs. 18.1%, without; p<0.001). For the residual anastomoses, only the use of Solomon technique was significantly associated with no residual anastomoses found after delivery.
Conclusions:
In addition to the use of Solomon technique, a lower incidence of rTTTS/TAPS was seen when 10 or 12 Fr cannulas were used. Decreased complication rates may be due to the use of scopes with better optics during placental mapping.
Objective:
To study fetal aortic isthmus (AoI) shunt dynamics in monochorionic (MC) twins.
Methods:
Normal and complicated MC pregnancies were prospectively enrolled. The relationship of isthmus flow index (IFI) with Doppler parameters of umbilical artery (UA), descending aorta (DAo), middle cerebral artery (MCA), and ductus venosus (DV), and with left and right ventricular cardiac output and stroke volume was studied.
Results:
The IFI was obtained in 180 examinations from 48 pregnancies (24 twin-twin-transfusion syndrome, TTTS; 4 selective intrauterine growth restriction, sIUGR; 12 TTTS+sIUGR; 8 uncomplicated). Median gestational age was 20.9 weeks. AoI diastolic flow was reversed in three cases. UA- and DV-PI z-scores were negatively correlated with the IFI (rs -0.40 and -0.26, respectively, p<0.001). Regression analysis identified only UA-PI as a determinant of the IFI (p<0.001). The IFI was significantly correlated with left ventricular cardiac output and stroke volume. It did not differ between TTTS donors and recipients. sIUGR fetuses had significantly lower IFI compared to normal-grown counterparts (p<0.001).
Conclusion:
In MC gestations, AoI shunting is predominantly determined by placental flow resistance, while cerebral impedance and volume status have no impact. In MC twins, the relationship between AoI flow and outcome deserves further study in the setting of sIUGR.
Mit der Zunahme der Anwendung von Reproduktionstechniken für die Behandlung von Subfertilitätsproblemen in einer Population von Frauen, in der sich gleichzeitig die Schwangerschaft immer mehr zum Ende des reproduktionsfähigen Alters verschiebt, hat die Anzahl von Mehrlingsschwangerschaften deutlich zugenommen (Black et al. 2010). Bei natürlich konzipierten Zwillingen kann davon ausgegangen werden, dass 2/3 der Zwillinge dizygot, und somit dichorial sind, und dass 1/3 monozygot sind. Von den monozygoten Zwillingen sind aufgrund einer frühen Teilung der Anlage 1/3 dichorial und aufgrund einer späteren Teilung 2/3 monochorial. Diese Proportionen scheinen sich aber durch den Einsatz der Reproduktionstechniken zu verändern, sodass ca. 95 % aller dadurch konzipierten Zwillinge dizygot und ca. 80 % aller monozygoten Zwillinge monochorial sind (Verstraelen et al. 2005). Insgesamt tragen die Geminigraviditäten nach einer Subfertilitätsbehandlung mit einer Verkürzung des Schwangerschaftsalters bei der Entbindung zu einem Anstieg der milden Frühgeburtlichkeit bei.
Twin-to-twin transfusion syndrome results from unbalanced vascular anastomoses in monochorionic twin gestations. This condition, affecting 2,500 pregnancies each year in the United States, is most commonly identified with ultrasonography on the basis of unequal amniotic fluid volumes in a monochorionic, diamniotic pregnancy. Hemodynamic alterations in the syndrome lead to oligohydramnios, intrauterine growth restriction, and frequently, anemia in the “donor” twin while the “recipient” has polyhydramnios and polycythemia. In severe cases, both twins are at risk of developing hydrops fetalis and death. The Quintero staging system is widely used to characterize the features and severity of the disease in a given pregnancy and to guide decisions regarding therapy. The advent of endoscopic fetoplacental surgery, which affords the possibility of laser photocoagulation of connecting placental vessels and thereby separation of the twins’ circulation, has revolutionized the management of this condition and improved outcomes. The main risk of intervention is preterm premature rupture of membranes and subsequent preterm delivery of the twins. The outcomes for survivors of the syndrome are generally comparable to those of monochorionic, diamniotic twins in general and relate primarily to the degree of prematurity.
Objective:
The primary objective of our study was to evaluate the long-term neurodevelopment outcome after laser surgery for twin-twin transfusion syndrome (TTTS). The secondary objective was to identify perinatal prognostic factors associated with neurodevelopmental impairment.
Method:
This was a single-center cohort prospective study carried out in pregnancies complicated by TTTS and treated by laser. Neurodevleopmental assesment included the administration of Ages and Stages Questionnaires® (ASQ), for the infants between two and five years of age.
Results:
A total of 187 patients underwent a laser for TTTS between 2004 and 2013. Significant brain lesions were detected in 8 (2.9%) cases by ultrasound and/or MRI including intraventricular hemorrhage, periventricular leukomalacia and porencephaly. Questionnaires were administered to 126 children (50.4%) at 24 months or older at the moment of testing. There were 13.5% of those infants who had an abnormal ASQ (established as 1 area or more scoring < 2SD) at 3.6 years +/- 1.3 follow-up. There was a higher rate of abnormal ASQ among the infants with a birth weight below the fifth percentile (p = 0.036).
Conclusion:
TTTS is associated with a risk of abnormal neurological development, even in case of laser surgery. Further studies are necessary to identify the risk factors for neurological impairment.
Objective
To assess the neurodevelopmental functions of survivors of twin-twin transfusion syndrome (TTTS) treated by fetoscopic laser coagulation (FLC), during the first year of life, comparing them to a control group; and to verify the influence of specific variables on neurodevelopment.
Method
This was a prospective, longitudinal study. The sample comprised 33 monochorionic diamniotic twins who underwent FLC for treatment of TTTS and 22 full-term infants of single-fetus pregnancies. Bayley Scales of Infant and Toddler Development Screening Test were used for evaluation. Prenatal, perinatal and postnatal information were obtained.
Results
There was an increased frequency of infants in the TTTS group with inadequate performance compared to the control group. The identified variables (fetal donor, low economic income and cardiorespiratory disease) negatively impacted expressive communication and fine motor skills.
Conclusion
Although through follow-up is recommended in all TTTS survivors, particular attention is required for the high-risk group as defined in this study.
Weltweit stellen sich rund 1,2% aller Schwangerschaften beim Menschen als Mehrlingsschwangerschaften dar. Die Häufigkeit von Mehrlingsschwangerschaften variiert allerdings stark je nach Region und Rasse, ebenso können Umweltfaktoren, saisonale Faktoren sowie familiäre Disposition die Häufigkeit von Mehrlingsschwangerschaften beeinflussen.
Purpose of review:
Twin-to-twin transfusion syndrome (TTTS) is an uncommon, but dangerous, complication of monochorionic diamniotic twin gestations. The purpose of this review is to provide an update on the evolving treatments in TTTS as it pertains primarily to laser photocoagulation, as well as to provide recently published information on outcomes.
Recent findings:
The Solomon laser technique, in which selective fetoscopic laser photocoagulation is first performed and then followed by laser of the vascular equator from one side of the placenta to the other, reduces TTTS complications of twin anemia-polycythemia syndrome and recurrent TTTS. The addition of fetal echocardiography to the historical staging of TTTS adds important information that may guide future therapies. The postlaser ablation rate of neurodevelopmental delay in TTTS has recently been reported to be 14%. Cotwin demise is a significant complication of untreated TTTS and survival carries a 25% risk of cystic periventricular leukomalacia, middle cerebral artery infarction, and injury to other central nervous system structures as noted by neuroimaging.
Summary:
Laser therapy for TTTS is clearly the only therapy that halts the disease process, allows both fetuses an opportunity to survive and protects a surviving cotwin in the event of the demise of one twin. Laser techniques have evolved greatly over the last 25 years and recent reports with the addition of the Solomon technique appearing to reduce some postlaser complications (twin anemia-polycythemia sequence and recurrent TTTS). Future focus of TTTS therapy should be centered on understanding the pathophysiology of the disease better with improvement in staging of the disease and on comparison of different laser techniques with the overall goal of not only increasing twin survival rates but also reducing long term neurodevelopmental morbidity.
Background
EmbryologyDetermining the amnionicity/chorionicity in twinsDichorionic/diamniotic (DC/DA) twinsMonochorionic/diamniotic (MC/DA) twinsReferences
During the last decades multiple birth rates increased remarkable. Actually the multiple birth rate in the US is 3.2 %, in Germany 3.43 % and in Austria 3.42 %. Chorionicity but not zygosity is the main determining factor regarding pregnancy outcome. Besides complications concerning all multiple pregnancies, monochorionic twins can develop unique problems like "Twin-to-Twin Transfusion Syndrome" (TTTS), "Twin Anemia-Polycythemia Sequence" (TAPS) and "Twin Reversed Arterial Perfusion Sequence" (TRAP Sequence).
The laser photocoagulation of communicating vessels has decreased the fetal mortality rate in the monochorionic pregnancies complicated by Twin-to-Twin Transfusion Syndrome. The technique of photocoagulation has been changing from the time of its implementation. The aim of the study was to compare the results of treatment with the use of "Quintero technique" (coagulation of arterial side of the anastomoses) and "modified technique" (coagulation of the recipient's side sparing the blood flow from donor to the placental lobe). Survival of at least one twin and survival of donor was similar in the group of 26 patients treated with the Quintero technique (85% and 42%) and in the group of 28 women treated with the modified technique (79% and 54%). Cerebral Palsy incidence was much higher in the group of Quintero technique (36%) when compared to 0% in the group of modified technique (χ 2 Pearson test, p = 0.01). Coagulation of artery from donor prevents transfusion of the blood to the recipient, but excludes the lobe from the donor's placental volume as well, even with present small donor's veins. Closing vein of the recipient instead of the donor's artery increases the donor's placental volume remaining after surgery and decreases the risk of Cerebral Palsy.
Introduction In the United States in 2004, 3.4% of all births were multiple births. Between 1994 and 2004, the multiple birth ratio in the United States increased by 32% (from 2.6% to 3.4%), largely due to increased use of assisted reproductive technology. This increase in multiple birth rates has had a tremendous impact on prematurity. In 2004, one in eight babies (12.5% of live births) was born prematurely; and of multiple gestations, 61.4% were born preterm, 58.5% were low birthweight (less than 2500 g), and 11.5% were very low birthweight (less than 1500 g). Infants from multiple gestations thus carry a tremendous economic burden, in 2005 the annual cost of prematurity in the United States was well over $26 billion. Among multiple gestations, the highest incidence is contributed by twins. Besides prematurity, twins, regardless of type, are at higher risk for neurological injury. Over the years, several studies have correlated cerebral palsy with multiple gestations. A recently published large case–control study based on the Swedish Medical Birth Registry between 1984 and 1998 showed a 1.4 odds ratio (95% CI 1.1–1.6) of cerebral palsy in twin gestations relative to their singleton counterparts. Besides their effect on society, twins pose interesting and challenging diagnostic and management dilemmas. From conception to delivery, and even beyond, twin gestations behave remarkably differently from their singleton counterparts, and have a myriad of unique physiologic changes and pathologic conditions that one must consider when caring for these special pregnancies.
Introduction Perinatal hypoxia–ischemia (HI) and asphyxia due to umbilical cord prolapse, delivery complications, airway obstruction, asthma, drowning, and cardiac arrest are significant causes of brain damage, mortality, and morbidity in infants and young children. The incidence of HI encephalopathy (HIE), for example, is ∼ 2 to 4/1000 live term births. Term infants that experience episodes of asphyxia can have damage in the brainstem and forebrain, with the basal ganglia, particularly the striatum, and somatosensory systems showing selective vulnerability. Infants surviving with HIE can have long-term neurological disability, including disorders in movement, visual deficits, learning and cognition impairments, and epilepsy. Many of these neurological disabilities are contributors to the complex clinical syndrome of cerebral palsy. Neuroimaging studies of full-term neonates and experimental studies on animal models suggest that this pattern of selective vulnerability is related to local metabolism and brain regional interconnections that instigate and propagate the damage within specific neural systems. This idea has been called the “metabolism-connectivity concept”. The neurodegeneration is partly triggered by excitotoxic mechanisms resulting from excessive activation of excitatory glutamate receptors and oxidative stress. The ion channel N-methyl-d-aspartate (NMDA) receptor and intracellular signaling networks involving calcium, nitric oxide synthase (NOS), mitochondria, and reactive oxygen species (ROS), such as superoxide, nitric oxide (NO), peroxynitrite, and hydrogen peroxide (H2O2), appear to have instrumental roles in the neuronal cell death leading to perinatal HIE.
The cultural modifications in women’s reproductive strategies over the past 50 years have drastically influenced the demographic scenario. Higher levels of education and a desire for economic and social success, as well as difficulties in finding a permanent job, have played a major role in modifying the reproductive strategies, as evidenced by delayed parenthood and the reduction in family size [1]. In addition to this expected twinning rate due to advancing maternal age, there is also evidence that natural twinning has increased in women who have been exposed to assisted reproduction technologies [2].
Objective:
To assess the neurodevelopmental functions (cognition, language and motor function) of survivors of twin-twin transfusion syndrome (TTTS).
Method:
Observational cross-sectional study of a total of 67 monochorionic diamniotic twins who underwent fetoscopic laser coagulation (FLC) for treatment of TTTS. The study was conducted at the Center for Investigation in Pediatrics (CIPED), Universidade Estadual de Campinas. Ages ranged from one month and four days to two years four months. Bayley Scales of Infant and Toddler Development Screening Test-III, were used for evaluation.
Results:
Most children reached the competent category and were classified as having appropriate performance. The preterm children scored worse than term infants for gross motor subtest (p = 0.036).
Conclusion:
The majority of children reached the expected development according to their age. Despite the good neurodevelopment, children classified at risk should be monitored for development throughout childhood.
Spasticity in cerebral palsy (CP) patients is a critical factor preventing voluntary movement, and can also be associated with involuntary clonus. Low reactive-level laser therapy (LLLT) has been reported as having good overall efficacy in CP patients and also in controlling clonus. The present study was designed to evaluate LLLT in the clinical setting to attenuate spasticity in severely handicapped CP patients. We treated 20 CP patients with near infrared (830 nm) LLLT (16.2J/cm2/point, once/week over 10 weeks) as a clinical study at our university hospital and a hospital connected with our university. For spasticity of the hip adductor muscle, the obturator nerve was the target for LLLT, and the tibial nerve was irradiated in the case of triceps surae muscle spasticity. LLLT was indicated for the 10 sessions and the degree of attenuation of spasticity was assessed after the final session. Some degree of efficacy and treatment latency was seen in 14 (70%) of the 20 patients, 5 evaluated as excellent, 6 as very good and 3 as fair. Little or no change was seen in the remaining 6 patients, and in no patient did the symptoms worsen. We concluded that LLLT was an efficacious treatment option in the conservative treatment of CP patients, that it was easilyapplied, non-invasive and pain-free, and that it did not have any adverse side effects.
Fetal interventions have clearly decreased mortality, but the neurological outcomes of survivors are of critical concern. Here we consolidated available data on long-term neurological outcomes after common fetal interventions to guide counseling, management, and future research.
Published studies assessing long-term neurological outcomes after common fetal interventions from 1990 through 2014 were collected. We included all studies with a cohort of more than 5 patients and with follow-up of 1 year or longer. We divided procedures into those performed for singletons and for multiples. Singleton procedures included amnioinfusion for preterm premature rupture of membranes, intrauterine transfusion for red cell alloimmunization-associated anemia, intrauterine transfusion for parvovirus-associated anemia, vesicoamniotic shunts, thoracoamniotic shunts, ventriculoamniotic shunts, fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia, and open fetal cases by myelomeningocele and others. Multiple procedures included those done for monochorionic twins including serial amnioreduction, selective fetoscopic laser photocoagulation, and selective termination.
Of 1341 studies identified, 28 met the inclusion criteria. We combined available literature for all procedures. Studies varied in their length of follow-up and method of assessing neurological status. Neurological outcome after intervention varied by procedure but was normal in 40-93%, mildly impaired in 3-33%, and severely impaired in 1-40%. Follow-up to school age was rare with the exception of procedures for monochorionic twins.
Fetal treatments have been successful in achieving survival in previously hopeless cases, but success should also be determined by the outcomes of survivors. Except for monochorionic twins, there is a dearth of reported long-term outcomes. Standardized reporting of long-term neurological sequelae is imperative so that meaningful analysis and study comparisons can be made.
Copyright © 2015 Elsevier Inc. All rights reserved.
Background:
Laser therapy is now a well recognised treatment for twin-to-twin transfusion syndrome (TTTS). We investigated the early childhood neurodevelopmental outcome of children post laser treatment for TTTS in our centre.
Methods:
Children of women who had laser therapy for TTTS between March 2006 and June 2008 were assessed at 30-69 months of age with WPPSI-III and a general health questionnaire. Major neurodevelopmental impairment (NDI) was reported as IQ<70 or cerebral palsy (CP). Borderline cognitive impairment was defined by IQ 70-79.
Results:
Amongst the 37 pregnancies treated, 62 infants were discharged home and the overall foetal survival rate was 84%. A total of 50 children (84%) from 31 pregnancies were assessed. Average age at assessment was 47 months. Two children with late treatment of congenital hypothyroidism were excluded. The majority of pregnancies were Quintero Stage III (74%). There was a significant trend for worse outcome with higher Quintero stage. The average gestational age at birth was 32 weeks. The majority (39, 78%) of children were found to be neurodevelopmentally normal; 9 (18%) had borderline cognitive development; and 2 (4%) had a major NDI, including one with cerebral palsy (2%).
Conclusions:
There was a modest level of neurocognitive impairment post laser therapy for TTTS, mainly borderline cognitive development, lesser so major NDI. There was a low incidence of cerebral palsy. Routine developmental and neurological follow-up of these children is recommended.
Objective
To determine the risk faxtors for spontaneous preterm delivery (sPTD) or preterm premature rupture of membranes <34 weeks gestation after fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS) and to identify the optimal threshold for pre-operative cervical length (CL).Study DesignSecondary analysis of prospectively collected data from 449 patients from 3 fetal centers was analyzed. CL measurements were obtained from pre-operative transvaginal ultrasound, between the gestational ages of 16–26 weeks. The risk factors associated with sPTD <34 weeks was determined using multivariate logistic regression. We excluded patients due to dual fetal demise and maternal or fetal indications for delivery without preterm premature rupture of membranes(n = 63). The optimal threshold for cervical length to predict sPTD <34 weeks was determined using receiver operator characteristics (ROC) curve and Youden index. Additionally, CL threshold for sPTD between 24 to 34 weeks, at every 2 weeks was determined.ResultssPTD <34 weeks occurred in 206 (53.4%) in the included patients. Only the pre-operative CL was significantly associated with sPTD. The pre-operative CL was normally distributed with a mean of 37.6 ± 10.3 mm (range 5–66 mm). Maternal age and parity were positively associated and gestational age at procedure and anterior placenta were negatively associated with cervical length on a multivariate linear regression. The area under the ROC curve for predicting sPTD with CL measurement was 0.61 (p = 0.02) and the optimal threshold was 28 mm with Youden index of 0.20 (sensitivity, and specificity of 92% and 27%, respectively). CL <25-28 mm increased risk for sPTD various all gestational age thresholds.ConclusionsPTD <34 weeks is associated with pre-operative CL < 28 mm. Preventive strategies should focus on this high-risk group.
Preterm birth after fetoscopic laser surgery for twin-twin transfusion continues to be a major challenge despite improved survival rates. The risk factors for the complications have been identified, which include preterm premature rupture of membranes, cervical length shortening, larger cannula diameter, amnioinfusion, complicated procedure, and severe disease. The interventions to prevent preterm birth such as cervical cerclage for short cervix and collagen plug placement have not been successful. Further understanding of the pathophysiology is urgently needed to identify newer methods to prevent preterm birth.
The purpose of this study was to evaluate the prognostic value of sonographic and clinical parameters to develop a staging classification of twin-twin transfusion syndrome (TTTS).
Severe TTTS was defined as the presence of polyhydramnios (maximum vertical pocket of > or = 8 cm) and oligohydramnios (maximum vertical pocket of < or = 2 cm). Nonvisualization of the bladder in the donor twin (-BDT) and absence of presence of hydrops was also noted. The middle cerebral artery, umbilical artery, ductus venosus, and umbilical vein in both fetuses were assessed with pulsed Doppler. Critically abnormal Doppler studies (CADs) were defined as absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein. TTTS was staged as follows: stage I, BDT still visible; stage II, BDT no longer visible, no CADs; stage III, CADs; stage IV, hydrops; stage V, demise of one or both twins. Laser photocoagulation of communicating vessels (LPCV) or umbilical cord ligation was performed depending on the severity of the condition. The study was approved by the Institutional Review Board of St. Joseph's Hospital in Tampa and by the Fetal Therapy Board at Hutzel Hospital, Detroit, and all patients gave informed consent.
A total of 80 of 108 referred patients met criteria for surgery, but only 65 were treated surgically: 48 with LPCV and 17 with umbilical cord ligation. Complete Doppler data were obtainable in 41 of 48 LPCV patients. Survival rates by stage for one or two fetuses were statistically different (chi-squared analysis = 12.9, df = 6, p = 0.044). Neither percent size discordance nor gestational age at diagnosis were predictive of outcome.
Staging of TTTS using the proposed criteria has prognostic significance. This staging system may allow comparison of outcome data of TTTS with different treatment modalities.
To compare the perinatal mortality and morbidity of infants with twin-twin transfusion syndrome (TTTS) with those of gestation matched twin controls and to assess the neurodevelopmental outcome of surviving twins with TTTS.
A cohort of 17 consecutive pregnancies with TTTS was enrolled over three years together with gestation matched twin pregnancies unaffected by TTTS. Serial amnioreduction for the TTTS pregnancies was performed as appropriate. Perinatal death and neonatal morbidities were recorded for both the TTTS cohort and controls. The TTTS survivors had neurodevelopmental follow up to at least 2 years of age.
In 12 of the pregnancies, serial amniocenteses were performed, but, in five, the infants were born before intervention. The mean gestational age at delivery was 29.1 weeks (range 23-36). There were five intrauterine deaths in the TTTS cohort and six neonatal deaths (survival 68%). In the control group, there was one intrauterine death and five neonatal deaths (survival 82%). Infants in the TTTS group had a greater requirement for inotropes (p = 0.04) and a higher incidence of renal failure (p = 0.005). Periventricular leucomalacia and cerebral atrophy were seen in 17% of the TTTS group, but none of the controls (p = 0.03). The 23 surviving TTTS infants were all followed up, with 22% having significant neurological morbidity: cerebral palsy and global developmental delay.
Twins with TTTS have high perinatal mortality and neonatal morbidity, and long term neurodevelopmental morbidity in survivors is high. Further investigation into the pathogenesis and management of TTTS is required.
Monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome at midgestation can be treated by either serial amnioreduction (removal of large volumes of amniotic fluid) or selective fetoscopic laser coagulation of the communicating vessels on the chorionic plate. We conducted a randomized trial to compare the efficacy and safety of these two treatments.
Pregnant women with severe twin-to-twin transfusion syndrome before 26 weeks of gestation were randomly assigned to laser therapy or amnioreduction. We assessed perinatal survival of at least one twin (a prespecified primary outcome), survival of at least one twin at six months of age, and survival without neurologic complications at six months of age on the basis of the number of pregnancies or the number of fetuses or infants, as appropriate.
The study was concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, because a planned interim analysis demonstrated a significant benefit in the laser group. As compared with the amnioreduction group, the laser group had a higher likelihood of the survival of at least one twin to 28 days of age (76 percent vs. 56 percent; relative risk of the death of both fetuses, 0.63; 95 percent confidence interval, 0.25 to 0.93; P=0.009) and 6 months of age (P=0.002). Infants in the laser group also had a lower incidence of cystic periventricular leukomalacia (6 percent vs. 14 percent, P=0.02) and were more likely to be free of neurologic complications at six months of age (52 percent vs. 31 percent, P=0.003).
Endoscopic laser coagulation of anastomoses is a more effective first-line treatment than serial amnioreduction for severe twin-to-twin transfusion syndrome diagnosed before 26 weeks of gestation.
Although cerebral palsy (CP) is the most common cause of motor deficiency in young children, it occurs in only a to 3 per 1000 live births. In order to monitor prevalence rates, especially within subgroups (birthweight, clinical type), it is necessary to study large populations. A network of GP surveys and registers was formed in 14 centres in eight countries across Europe. Differences in prevalence rates of GP in the centres prior to any work on harmonization of data are reported. The subsequent process to standardize the definition of CP, inclusion/exclusion criteria, classification, and description of children with CP is outlined. The consensus that was reached on these issues will make it possible to monitor trends in CP rate, to provide a framework for collaborative research, and a basis for services planning among European countries.
The twin-twin transfusion syndrome is a serious complication of monochorionic twin pregnancies. Partly as a result of an inadequate understanding of the pathophysiology of the syndrome, there is a lack of consensus in clinical management. We sought to review the available information on the etiology of twin-twin transfusion syndrome, to identify parameters that contribute to the severity of the syndrome, and propose a rational management plan based on pathophysiology, clinical presentation and the efficacy of therapies. We therefore amalgamated recent advances in twin-twin transfusion syndrome computer modelling and clinical studies, particularly on therapeutic outcomes. We found that the oligo-polyhydramnios sequence that defines twin-twin transfusion syndrome prenatally represents a wide continuum of severity in the imbalance between the fetoplacental circulations of both twins. In severe twin-twin transfusion syndrome cases, in which the circulatory imbalance deteriorates beyond fetal control, fetoscopic laser therapy of all anastomoses along the placental vascular equator is predicted to have significantly better survival rates and fewer neurological sequelae than amnioreduction. In contrast, mild twin-twin transfusion syndrome cases have better outcomes after one or at most a few amnioreductions than laser therapy, as a result of significantly fewer procedure-related risks. In conclusion, optimal individual therapy may possibly achieve an 85% survival rate in twin-twin transfusion syndrome, but requires advancement in non-invasive criteria that predict the severity of the syndrome. Identifying such criteria is a future challenge. For the interim, twin-twin transfusion syndrome diagnosed before 26 weeks' gestation has significantly better survival rates and fewer neurological sequelae after laser therapy than amnioreduction. Twin-twin transfusion syndrome diagnosed after 26 weeks can best be treated by amnioreduction, or delivery. Contrary to previous claims, fetoscopic laser therapy has outgrown its experimental status. Although improvements in technique and technology are likely, laser placental ablation has a firm scientific and clinical basis.
The evaluation of 2 cases of twin transfusion syndrome by conventional and real-time B-scan ultrasound is described. The importance of differentiating this syndrome from the isolated growth failure of 1 fetus in a twin pregnancy with a normally developing second fetus is emphasized. Assessment of placentation, fetal size and activity, as well as amount of fluid by diagnostic ultrasound is an important aid in the management of multiple gestation. © 1981 The American College of Obstetricians and Gynecologists.
1.Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism.
2.These ‘programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension.
3.This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.
Advances in perinatal care have improved the chances for survival of extremely low birthweight (< 800 g) and gestational age (< 26 weeks) infants. A review of the world literature and our own experience reveals that at 23 weeks gestation survival ranges from 2% to 35%. At 24 weeks gestation the range is 17% to 58%, and at 25 weeks gestation 35% to 85%. Differences in population descriptors, in the initiation and withdrawal of treatment and the duration of survival considered may account for the wide variations in the reported ranges of survival. Major neonatal morbidity increases with decreasing gestational age and birthweight. The rates of severe cerebral ultrasound abnormality range at 23 weeks gestation from 10% to 83%, at 24 weeks from 17% to 64% and at 25 weeks gestation from 10% to 22%. At 23 weeks gestation, chronic lung disease occurs in 57% to 70% of survivors, at 24 weeks in 33% to 89%, and at 25 weeks gestation in 16% to 71% of survivors. When compared to children born prior to the 1990's, the rates of neurodevelopmental disability have, in general, remained unchanged. Of 30 survivors reported at 23 weeks gestation nine (30%) are severely disabled. At 24 weeks gestation the rates of severe neurodevelopmental disability (including subnormal cognitive function, cerebral palsy, blindness and deafness) range from 17% to 45%, and at 25 weeks gestation 12% to 35% are similarly affected. In Cleveland, Ohio, we compared the outcomes of 114 children with birthweight 500-749 g born 1990-1992 to 112 infants born 1993-1995. Twenty month survival was similar (43% vs 38%). The use of antenatal and postnatal steroids increased (10% vs 54% and 43% vs 84%, respectively, P< 0.001), however the rates of chronic lung disease increased from 41% to 63% (P = 0.06). There was a significant increase in the rate of subnormal cognitive function at 20 months corrected age (20% vs 48%, P < 0.02) and a trend to an increase in the rate of cerebral palsy (10% vs 16%) and neurodevelopmental impairment. We conclude that, with current methods of care, the limits of viability have been reached. The continuing toll of major neonatal morbidity and neurodevelopmental handicap are of serious concern.
We have performed fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in previable pregnancies affected by twin-twin transfusion syndrome (TTTS) since 1988. Treatment outcomes obtained after the procedure's learning curve are presented and compared to those from other centers performing FLOC or other treatment methods.
A total of 100 cases of FLOC have been performed at our centers. The later 67 TTTS patients had a mean gestational age of 21.1 +/- 1.7 weeks (range 18-24.5) with a mean fundal height of 33.1 +/- 4.9 cm (range 27-44) when treated. Eighteen (27%) had failed another treatment method before FLOC.
All 67 cases have delivered with 82% (55/67) having at least one surviving twin and 93/134 (69%) of the twins surviving overall. Thirty-eight have surviving twins, 17 have one survivor (5 neonatal and 12 fetal deaths), and 12 have none. The mean duration of pregnancy following FLOC was 9.9 +/- 5.5 weeks (range 1.0-19). Only 4 of 93 (4.3%) survivors have significant handicaps at a mean follow-up of 14.3 +/- 10.1 months (range 1.0-34).
Fetoscopic laser occlusion of chorioangiopagous vessels within the vascular equator limits the duration of fetal pathophysiology in TTTS and results in neonatal outcomes superior to the modified procedure and other treatment methods.
Advances in perinatal care have improved the chances for survival of extremely low birthweight (<800 grams) and gestational age (<26 weeks) infants. A review of the world literature reveals that among regional populations, survival at 23 weeks' gestation ranges from 2 to 35%, at 24 weeks' gestation 17 to 62% and at 25 weeks' gestation 35 to 72%. These wide variations may be accounted for by differences in population descriptors, in the criteria used for starting or withdrawing treatment, in the reported duration of survival and differences in care. Major neonatal morbidity increases with decreasing gestational age and birthweight. At 23 weeks' gestation, chronic lung disease occurs in 57 to 86% of survivors, at 24 weeks in 33 to 89% and at 25 weeks' gestation in 16 to 71% of survivors. The rates of severe cerebral ultrasound abnormality range from 10 to 83% at 23 weeks' gestation, 9 to 64% at 24 weeks and 7 to 22% at 25 weeks' gestation Of 77 survivors at 23 weeks' gestation, 26 (34%) have severe disability (defined as subnormal cognitive function, cerebral palsy, blindness and/or deafness). At 24 weeks' gestation, the rates of severe neurodevelopmental disability range from 22 to 45%, and at 25 weeks' gestation 12 to 35%. When compared with children born prior to the 1990s, the rates of neurodevelopmental disability have, in general, remained unchanged. We conclude that, with current methods of care, the limits of viability have been reached. The continuing toll of major neonatal morbidity and neurodevelopmental handicap are of serious concern.
The purpose of this study was to determine long-term outcomes among pregnancies complicated by twin-twin transfusion syndrome and treated in a tertiary center with serial aggressive amnioreduction.
Thirty-three pregnancies with a diagnosis of twin-twin transfusion syndrome were treated with > or =1 amnioreduction. The perinatal outcome was assessed according to 15 parameters, whereas the main outcome at age > or =2 years was the absence of cerebral palsy.
Gestational age at diagnosis ranged from 14.5 to 33 weeks' gestation (median, 20.6 weeks' gestation), whereas gestational age at delivery was between 18.5 and 37 weeks' gestation (median, 30.5 weeks' gestation). The number of amnioreductions per pregnancy ranged from 1 to 15 (median, 2). At initial examination hydrops of the recipient and absence of the end-diastolic velocity of the umbilical artery in one of the twins were associated with poor prognosis. Fifty-one (77%) twins were born alive. At 24 months after birth both infants from 57% of the pregnancies (19/33) were alive, whereas at least one infant from 70% of the pregnancies (23/33) was alive. Thirty-three infants (78% of the survivors) were older than 36 months at last follow-up. Cerebral palsy was diagnosed in 2 of 42 infants (4.7%). One of the affected infants was born after the fetal death of the cotwin; the other infant was born with congenital cardiac malformations.
In the group of fetuses in which both twins were delivered alive after 27 weeks' gestation without congenital malformations and survived the neonatal period, no major neurologic handicaps developed in any of the infants. At initial examination both hydrops of the recipient and absence of end-diastolic flow velocity waveforms of the umbilical artery in one of the twins were poor prognostic signs.
The purpose of this study was to determine the neurodevelopmental risks in patients with twin-to-twin transfusion syndrome, a rare but serious complication of monochorionic twin gestations. From a total sample of 94 twins with twin-to-twin transfusion syndrome, admitted during 1989 and 1993, 49 patients survived and 40 patients were followed to a mean age of 24 months. Neurological status and psychomotor development (Denver and Griffiths Developmental Tests) were determined. Parameters of the neonatal period were evaluated for their potential prediction. Of the 40 tested patients 18 showed a normal psychomotor development. Thirteen patients exibited a specific delay in language development and/or showed minor neurological dysfunctions. Nine twins had severe psychomotor retardation in combination with cerebral palsy. Major neurological sequelae were found, more common in recipients than in donors (6/19 vs 3/21). Correspondingly, neonatal ultrasound showed more pathological results (especially periventricular leucomalacia) in recipients. Neither anaemia nor polycythaemia at birth can predict developmental outcome. Apart from a high prenatal mortality rate, both twins, donators as well as recipients, are highly at risk for brain damage of different aetiology, associated with abnormal neonatal cerebral ultrasound.
Serial aggressive amnioreduction is the most widely used therapy for pregnancies that are complicated by twin-twin transfusion syndrome. Survival rates reported with this therapy are 33% to 83%, the wide range attributable to the small number of patients in these case series. Similarly, data on morbidity in survivors are imprecise. We instituted the international twin-twin transfusion syndrome registry to determine the perinatal survival and morbidity rates and the factors that influence perinatal outcome in patients with twin-twin transfusion syndrome who were treated with serial aggressive amnioreduction from 1990 to 1998.
A total of 223 sets of twins who were diagnosed with twin-twin transfusion syndrome before 28 weeks' gestation from 20 fetal medicine referral centers were analyzed, with follow-up data until 4 weeks after birth.
Three hundred forty-six twins (78%; 182 recipients and 164 donors) were born alive. Two hundred sixty-six twins (60%; 144 recipients and 122 donors) were alive 4 weeks after birth. Both fetuses survived to 4 weeks in 108 pregnancies (48.4%), whereas, at least 1 fetus survived in 158 pregnancies (70.8%). The interval between the last amnioreduction and delivery ranged from zero to 138 days (median, 17.5 days). In the infants who survived to 4 weeks after birth, abnormalities on neonatal cranial scan were diagnosed in 24% of recipients and in 25% of donors. Logistic regression analysis indicated that the survival rate was significantly related to gestational age at diagnosis, presence of end-diastolic blood flow in the umbilical artery velocity waveforms, presence of hydrops, mean volume of amniotic fluid removed per week, larger birth weight, and gestational age at delivery. The hemoglobin level difference at birth was the only significant parameter to predict abnormal cranial ultrasonography in newborns.
These data document perinatal survival and neonatal morbidity rates in severe twin-twin transfusion syndrome that were treated by serial aggressive amnioreduction. Outcome was influenced by several perinatal risk factors, which may be used to counsel patients before and during therapy.
To examine the postnatal development of a group of children born after in utero laser ablation therapy for severe twin-to-twin transfusion syndrome.
Retrospective cohort outcome study involving assessment of neurodevelopment and physical well being.
Harris Birthright Centre, King's College Hospital, London.
Twins and singleton survivors treated via laser ablation therapy for twin-to-twin transfusion syndrome over a four-year period.
Of 54 families contacted to participate in the study, who had been treated for twin-to-twin transfusion syndrome during a four-year period, 24 families attended for paediatric assessment; 12 pairs of twins and 12 singleton survivors were assessed for perinatal, neurological and neurodevelopmental outcome using the Griffiths scales of mental development. A further 20 families were assessed via a proforma after contact with their general practitioner. A comparison of these groups showed no significant differences in sociodemographic factors or severity of disease between responders (44 families, 81.5%) and non-responders (10 families).
The group of children assessed by a paediatrician had low birthweight (1619g donor, 1814g recipient, 1877g singleton) and had been born preterm (33 weeks twins, 31.2 weeks singleton) with attendant increased resuscitation, neonatal unit admission (mean 40 days) and instrumental delivery. Mean Griffiths scores were within the normal range of ability (91.2 donor vs 97.7 recipient and 101.6 singletons) with the only significant difference being in the locomotor subscale where donor (82.6) and recipient (85.3) were less than singletons: -99.1 (P < 0.05). There was no cerebral palsy in the singleton survivors, but there were five cases in the twin group. All except one affected child (with quadriplegia) had mean Griffiths scores in the normal range. In the GP proforma group there was one case, in a twin, of cerebral palsy.
The overall cerebral palsy rate was 9%: 0% in the singleton survivors group and 13.3% in the twin survivors group. This pilot data highlights the need for careful long term follow up of children affected by twin-to-twin transfusion syndrome.
To validate an established staging system for twin-twin transfusion syndrome.
Prospective observational study in a tertiary referral fetal medicine center of 52 consecutive cases of twin-twin transfusion syndrome. Each pregnancy was assessed longitudinally for a variety of prognostic factors including fetal biometry, amniotic fluid volume, arterial and venous Doppler sonogram abnormalities, and the presence of hydrops. Data were used to determine stage at diagnosis and first treatment, and worst stage throughout pregnancy. Perinatal outcome was assessed by stage. Management comprised serial amnioreduction, septostomy, selective reduction, or delivery, alone or in combination.
Median gestation at presentation and first treatment were both 21 weeks (range 14-34 and 15-34), and at delivery it was 29 weeks (range 16-40). Sixty-three percent of pregnancies (33 of 52) were at least stage III at presentation. Forty-five percent of pregnancies (22 of 49) progressed to a more advanced stage. Overall survival was 47% (47 of 100), with no difference between donor and recipient fetuses (40% [20 of 50] versus 54% [27 of 50] [chi(2) P =.5]). Survival rates were 58% (15 of 26), 60% (six of ten), 42% (20 of 48), 43% (six of 14), and 0% (none of two) for stages I-V, respectively, with no significant influence of stage at presentation on survival. Survival was poorer where stage increased, versus decreased (27% [12 of 44] versus 94% [17 of 18] chi(2) P <.001). Kaplan-Meier survival curves indicated that staging at presentation identified pregnancies at greater risk of earlier rather than later gestational perinatal loss.
The Quintero staging system did not distinguish good from bad outcome at presentation, and thus should be used with caution in guiding initial management of twin-twin transfusion syndrome. However, prognosis was influenced by a change in stage, and pregnancies progressing to higher stage disease were at increased risk of earlier perinatal loss. Staging may thus be more useful in monitoring disease progression.
To relate prenatal data of monochorionic pregnancies complicated by Twin-Twin transfusion syndrome (TTTS) with survival rates and neurological morbidity.
Thirty-two cases of TTTS underwent biweekly ultrasound examinations. Amnioreduction was the standard of care. Mortality and neurological morbidity were evaluated; the children had neurodevelopmental follow-up with a mean follow-up time of 24 months.
Ten out of 32 pregnancies terminated before 24 weeks of gestation, six after induction and four after spontaneous abortion. Among the 22 pregnancies followed up after 24 weeks, the overall survival rate at 28 days was 70% (31/44) with 10 intrauterine deaths including three cases of single selective terminations, and with three neonatal deaths. Eighteen out of 31 babies (58%) had a normal neurological development, eight cases had major and five cases minor neurological disabilities. Neonatal survival was not related to gestational age at diagnosis, number of amnioreductions or weeks at delivery. Absence of end diastolic flow in the umbilical artery, either in the donor or the recipient twin, and birth weight <1000 g were both associated with a higher perinatal mortality. Number of amnioreductions (>2) and birth weight <1000 g were both associated with abnormal neurological follow-up.
In TTTS, absent end diastolic flow in the umbilical artery and birth weight can predict perinatal survival; neurological development is correlated with number of amnioreductions and birth weight.
The purpose of this study was to investigate long-term neurodevelopmental outcome after intrauterine laser treatment for twin-twin transfusion syndrome.
All 89 surviving infants who were treated between January 1995 and May 1997 were investigated in a single center. Seventy-five children were tested with the Griffiths' Developmental Test Scales at a median age of 21 months; 14 children (median age, 34 months) were tested with the Snijders-Oomen-Non-Verbal-Intelligence Test. All children underwent a detailed standardized physical and neurologic examination.
Sixty-nine infants (78%) showed a normal development (group I), 10 infants (11%) had minor neurologic deficiencies (group II), and 10 infants (11%) had major neurologic deficiencies (group III). No difference between recipient and donor status was observed (P =.93). There was a trend toward a more favorable outcome for those infants who were born as twins (53 infants [81%] in group I and 5 infants [8%] in group III) compared with singleton survivors after intrauterine death of the cotwin (16 infants [67%] in group I and 5 infants [21%] in group III); however, the difference was not significant (P =.12).
After intrauterine laser treatment for twin-twin transfusion syndrome, 78% of the children had a normal neurodevelopmental status, 11% of the children had minor neurologic deficiencies, and 11% of the children had major neurologic deficiencies, at a median age of 22 months.
The purpose of this study was to determine the long-term neurodevelopmental outcome in children after twin-to-twin transfusion syndrome.
Maternal and neonatal medical records of all twin-to-twin transfusion syndrome patients who were admitted to our center between 1990 and 1998 were reviewed. Neurologic and mental development at school age was assessed during a home visit in all twin-to-twin transfusion syndrome survivors.
A total of 33 pregnancies with twin-to-twin transfusion syndrome were identified. Four couples opted for termination of pregnancy. All other pregnancies were treated conservatively, 18 pregnancies (62%) with serial amnioreductions and 11 pregnancies (38%) without intrauterine interventions. Mean gestational age at delivery was 28.6 weeks (range, 20-37 weeks). The perinatal mortality rate was 50% (29/58 infants). The birth weight of the donor twins was less than the recipient twins (P<.001). Systolic blood pressure at birth was lower in donors than in recipients (P=.023), and donors required inotropic support postnatally more frequently than did recipients (P=.008). The incidence of hypertension at birth was higher in recipients than in donors (P=.038). Abnormal cranial ultrasonographic findings were reported in 41% of the neonates (12/29 neonates). All long-term survivors (n=29 neonates) were assessed during a home visit. Mean gestational age at birth of the surviving twin was 31.6 weeks (range, 25-37 weeks). The mean age at follow-up was 6.2 years (range, 4-11 years). The incidence of cerebral palsy was 21% (6/29 infants). Five of 6 children with cerebral palsy had an abnormal mental development. The incidence of cerebral palsy in the group of survivors who were treated with serial amnioreduction was 26% (5/19 infants). Four children were born after the intrauterine fetal demise of their co-twin, 2 of which had cerebral palsy.
The incidence of adverse neurodevelopmental outcome in twin-to-twin transfusion syndrome survivors is high, especially after the intrauterine fetal demise of a co-twin.
Severe mid-trimester twin-twin transfusion syndrome (TTS) complicates about 15% of monochorionic twin pregnancies. If left untreated, the mortality is 80-100%. The pathophysiological prerequisite for the onset of TTS is unequal blood flow via arteriovenous placental anastomoses from the so-called donor to the recipient twin. This can result in hypovolemia, hypotension and oligo- or anuria in the donor, and hypervolemia, hypertension, polyuria and finally heart failure in the recipient. Leading sonographic signs of TTS include severe oligo- or anhydramnios and a small or absent bladder filling in the donor in contrast to polyhydramnios with increased bladder filling in the recipient. Patients might present with clinical symptoms due to massive polyhydramnios. In severe mid-trimester TTS, fetoscopic laser occlusion of the anastomosing vessels on the placental surface under local anaesthesia plus subsequent amniodrainage is the most promising therapeutic option at present. In acute TTS after 26 weeks of gestation, amniodrainage is the therapy of choice. All patients suspected of this high-risk condition should be referred to a specialized fetal medicine centre.
To assess long term outcomes of children from pregnancies complicated by twin-to-twin transfusion syndrome.
Comparison of children from pregnancies with twin-to-twin transfusion syndrome in Western Australia with a contemporaneous regional comparison cohort of preterm and term infants studied using an identical assessment procedure.
All infants aged > or =18 months were identified from a geographically based longitudinal cohort of monochorionic twin pregnancies with an antenatal diagnosis of twin-to-twin transfusion syndrome conducted prospectively since 1992.
Children were evaluated using age-specific developmental and behavioural assessments. Cerebral palsy was diagnosed clinically and ascertainment confirmed through the Western Australian Cerebral Palsy Register.
Intellectual disability, cerebral palsy, behavioural and cognitive function.
Fifty-two children were identified as eligible for study and assessments were performed on 49 (94%). Three surviving children had a diagnosis of cerebral palsy (5.8%). The mean IQ score was 8 points lower in twin-to-twin transfusion syndrome children compared with the comparison cohort although this was mainly due to a decrement of 13 points in those born before 33 weeks of gestation. There was no difference between the donor and the recipient twin in terms of IQ scores (median difference -3, 95% CI -9 to 6). There was no relationship of IQ score to the worst stage of the twin-to-twin transfusion syndrome. Child Behavior Check List and Vineland Adaptive Behavior Scale scores did not differ between twin-to-twin transfusion syndrome children and the comparison group.
Twin-to-twin transfusion syndrome is associated with a significant reduction in IQ score in very preterm survivors. There seems to be no increase in the prevalence of cerebral palsy. Overall behaviour and adaptive behaviour scale scores are similar to a comparison group.
This study was undertaken to investigate long-term neurodevelopmental outcome of children born after intrauterine laser coagulation for severe twin-twin transfusion syndrome.
One hundred sixty-seven surviving infants treated between June 1997 and September 1999 were investigated at a median age of 3 years and 2 months. All children underwent a detailed standardized physical and neurologic examination and a standardized developmental test (Griffiths' Developmental Test Scales and Snijders-Oomen Non-Verbal-Intelligence Test).
One hundred forty-five infants (86.8%) showed normal development, 12 infants (7.2%) showed minor neurologic abnormalities, and 10 infants (6.0%) major neurologic abnormalities. There was no difference in outcome for the former donors/recipients (P = .349) and between infants who were born as twins or singletons (P = .088).
With a high rate (86.8%) of normal neurodevelopmental outcome and an incidence of only 6.0% of major neurologic deficiencies, intrauterine laser coagulation seems to be the best treatment option for severe twin-twin transfusion syndrome.
The objective of the study was to determine the incidence, origin, and character of cerebral lesions in monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.
This was a prospective study of monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery and monochorionic twins without twin-to-twin transfusion syndrome delivered at our center between June 2002 and September 2005, using cranial ultrasonography.
Incidence of antenatally acquired severe cerebral lesions in the twin-to-twin transfusion syndrome group was 10% (8/84) and 2% (2/108) in the non-twin-to-twin transfusion syndrome group (P = .02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in the twin-to-twin transfusion syndrome group and 6% (6/108) in the non-twin-to-twin transfusion syndrome group (P = .04). Antenatal injury was responsible for severe cerebral lesions in 67% (8/12) of the twin-to-twin transfusion syndrome group.
Incidence of severe cerebral lesions in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery is high and results mainly from antenatal injury.
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