Surveillance and management of TTTS and TRAP in MCDA twins

Multiple pregnancies pose unique challenges for many obstetricians. The average number of children in families has drastically reduced and women tend to decide to have children later in life than even a few decades ago. These facts mean, that the time window to have children is getting ever shorter and also that the number of twin and higher-grade multiple pregnancies continues to rise. As soon as the diagnosis of chorionicity of a multiple pregnancy is made clear guidelines should be followed for counseling, surveillance and for possible management of eventual complications. These guidelines have evolved over the last 10–15 years to a level, where early diagnosis, individual counseling are possible. In these cases timely referral to a management center can signifi cantly improve the survival rates of these pregnancies. It cannot be emphasized often enough, that it is the chorionicity and not the amnionicity of a twin pregnancy, which determines the risks and therefore the management of these pregnancies. The root of all possible complications in monochorionic pregnancies are the random connection of fetal blood vessels on the placental surface, and also a similarly random and unequal sharing of the placenta. Depending on the combination of these factors different pathologic conditions can occur. In case of subacute and acute AV anastomosis the classic twin-to-twin transfusion occurs. This is a massive volume shift between the twins. This happens in about 10% of al MCDA pregnancies. The trusted staging system recommended by Quintero helps us to assess the stage of the disease. The only causal therapy for TTTS is the functional di-chorionising of the placenta. This is done by coagulating the abnormal placental vessels using LASER light. The majority of these procedures result in the survival of both, but at least one of the twins. When the blood exchange between the fetuses slowly and chronically occurs, we usually do not see signifi cant volume shift as in TTTS, but there is a considerable difference in the hemoglobin counts of the fetuses. This condition is called TAPS (twin-anemia- polycytemia-sequence). This condition can also be managed by fetoscopic laser photocoagulation, but as a reasonable alternative an intrauterine blood transfusion will be offered. The talk presents guidelines and recommendations for the evidence based surveillance and management of TTTS and TAPS in monochorionic pregnancies

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures

First-trimester screening between 11 + 0 and 13 + 6 weeks with qualified prenatal counseling, detailed ultrasound, biochemical markers and maternal factors has become the basis for decisions about further examinations. It detects numerous structural and genetic anomalies. The inclusion of uterine artery Doppler and PlGF screens for preeclampsia and fetal growth restriction. Low-dose aspirin significantly reduces the prevalence of severe preterm eclampsia. Cut-off values define groups of high, intermediate and low probability. Prenatal counseling uses detection and false-positive rates to work out the individual need profile and the corresponding decision: no further diagnosis/screening - cell-free DNA screening - diagnostic procedure and genetic analysis. In pre-test counseling it must be recognized that the prevalence of trisomy 21, 18 or 13 is low in younger women, as in submicroscopic anomalies in every maternal age. Even with high specificities, the positive predictive values of screening tests for rare anomalies are low. In the general population trisomies and sex chromosome aneuploidies account for approximately 70 % of anomalies recognizable by conventional genetic analysis. Screen positive results of cfDNA tests have to be proven by diagnostic procedure and genetic diagnosis. In cases of inconclusive results a higher rate of genetic anomalies is detected. Procedure-related fetal loss rates after chorionic biopsy and amniocentesis performed by experts are lower than 1 to 2 in 1000. Counseling should include the possible detection of submicroscopic anomalies by comparative genomic hybridization (array-CGH). At present, existing studies about screening for microdeletions and duplications do not provide reliable data to calculate sensitivities, false-positive rates and positive predictive values

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is &lt;10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical &amp; Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

Surveillance and management of TTTS and TRAP in MCDA twins

Multiple pregnancies pose unique challenges for many obstetricians. The average number of children in families has drastically reduced and women tend to decide to have children later in life than even a few decades ago. These facts mean, that the time window to have children is getting ever shorter and also that the number of twin and higher-grade multiple pregnancies continues to rise. As soon as the diagnosis of chorionicity of a multiple pregnancy is made clear guidelines should be followed for counseling, surveillance and for possible management of eventual complications. These guidelines have evolved over the last 10–15 years to a level, where early diagnosis, individual counseling are possible. In these cases timely referral to a management center can signifi cantly improve the survival rates of these pregnancies. It cannot be emphasized often enough, that it is the chorionicity and not the amnionicity of a twin pregnancy, which determines the risks and therefore the management of these pregnancies. The root of all possible complications in monochorionic pregnancies are the random connection of fetal blood vessels on the placental surface, and also a similarly random and unequal sharing of the placenta. Depending on the combination of these factors different pathologic conditions can occur. In case of subacute and acute AV anastomosis the classic twin-to-twin transfusion occurs. This is a massive volume shift between the twins. This happens in about 10% of al MCDA pregnancies. The trusted staging system recommended by Quintero helps us to assess the stage of the disease. The only causal therapy for TTTS is the functional di-chorionising of the placenta. This is done by coagulating the abnormal placental vessels using LASER light. The majority of these procedures result in the survival of both, but at least one of the twins. When the blood exchange between the fetuses slowly and chronically occurs, we usually do not see signifi cant volume shift as in TTTS, but there is a considerable difference in the hemoglobin counts of the fetuses. This condition is called TAPS (twin-anemia- polycytemia-sequence). This condition can also be managed by fetoscopic laser photocoagulation, but as a reasonable alternative an intrauterine blood transfusion will be offered. The talk presents guidelines and recommendations for the evidence based surveillance and management of TTTS and TAPS in monochorionic pregnancies

Maternal Complications and Hemodynamic Changes Following Intrauterine Interventions for Twin-to-Twin Transfusion Syndrome in Monochorionic Diamniotic Twin Pregnancies

Twin-to-twin transfusion syndrome (TTTS) is a challenging complication in monochorionic diamniotic (MCDA) twins. Intrauterine interventions, such as fetoscopic laser ablation and cord occlusion followed by amniodrainage, are established treatments. Little is known about maternal complications and hemodynamics following these interventions. We performed a retrospective analysis of maternal procedure-related complications and the impact of such procedures on maternal hemodynamics and blood characteristics. Within the study period, 100 women with severe TTTS treated by fetoscopic laser ablation (FLA) or cord occlusion (CO) were identified. Clinically relevant maternal complications were reported in four (4%) cases. There was a significant decrease in hemoglobin, hematocrit, and albumin between admission and postoperative measurements (all p &lt; 0.001). Systolic and diastolic blood pressure, as well as maternal heart rate, decreased from time of skin suture to postoperative measurements (all p &lt; 0.001). Within a 24 h interval, there was a positive correlation between hematocrit (Spearman&#8217;s rho 0.325; p = 0.003), hemoglobin (Spearman&#8217;s rho 0.379; p &lt; 0.001), and albumin (Spearman&#8217;s rho 0.360; p = 0.027), and the amount of amniodrainage during the intervention. Maternal procedure-related complications are relatively rare. Significant hemodynamic alterations and maternal hemodilution are common clinical findings following intrauterine interventions

Amniodrainage-Induced Circulatory Dysfunction in Women Treated for Twin-To-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies usually requires fetoscopic laser ablation (FLA) followed by amniodrainage (AD). Perioperative maternal hemodynamic changes and hemodilution have been observed. Little is known about the underlying pathophysiology. We aimed to evaluate the impact of high volume amniodrainage on intrauterine pressure, placental thickness and maternal blood characteristics. A total of 18 cases of TTTS were included in this prospective pilot study. All patients were treated with FLA and subsequent AD. Intrauterine pressure and placental thickness were assessed before, during and after amniodrainage. Maternal hemoglobin, hematocrit and serum albumin were measured at admission and 24 h after the intervention. Amniodrainage led to a decrease in mean intrauterine pressure (from 30.1 &plusmn; 8.1 mmHg to 17.6 &plusmn; 3.6 mmHg (p &lt; 0.001)) and an increase in mean placental thickness (from 16.8 &plusmn; 6.4 mm to 31.83 &plusmn; 8.64 mm (p &lt; 0.001)). There was a positive correlation between changes in placental thickness and the amount of amniodrainage during intervention (Pearson&rsquo;s Rho 0.73; p = 0.001). Hematocrit decreased from 33.4 &plusmn; 3.8 (%) to 28.4 &plusmn; 3.5 (%), i.e., an increase in relative blood volume by 18 &plusmn; 10.2% (p &lt; 0.001). Albumin decreased from 37.9 &plusmn; 0.9 g/L to 30.7 &plusmn; 2.2 g/L, i.e., an increase in relative plasma volume by 24 &plusmn; 8.1% (p &lt; 0.001). Amniodrainage leads to uterine decompression, increased placental thickness and subsequent maternal hemodilution. We propose the term &ldquo;amniodrainage-induced circulatory dysfunction&rdquo; for these specific maternal hemodynamic changes in the treatment of twin-to-twin transfusion syndrome

Screening, Management and Delivery in Twin Pregnancy

The following AWMF guideline (DGGG/AGG & DEGUM responsible) deals with the diagnosis, screening and management of twins as well as the timing and mode of birth.Twin pregnancies can be classified as dichorionic diamniotic (DC DA), monochorionic diamniotic (MC DA) and monochorionic monoamniotic (MC MA) which are always monochorionic.Twin pregnancies can be concordant (both twins are affected) or discordant (only one twin is affected) for chromosomal defects, malformations, growth restriction and hemodynamic disorders.Chorionicity is the prognostically most significant parameter. Monochorial twins have significantly higher risks of intrauterine morbidity and mortality compared to dichorial twins.In particular, general aspects of twin pregnancies such as dating, determination of chorionicity and amnionicity, the labeling of twin fetuses and the perinatal switch phenomenon are discussed.Routine monitoring of MC and DC twin pregnancies with ultrasound at 11-13+ 6 weeks of gestation for chromosomal defects, invasive prenatal diagnosis, first-trimester NT or CRL discrepancies, early diagnosis of fetal anatomical defects, and management of twins with abnormalities, including selective fetocide, is described.Second trimester screening and management for preterm birth, intrauterine selective growth restriction (sFGR), classification of monochorial twins with sFGR, and management of the surviving twin after the death of the co-twin are described.Complications exclusively affecting MC twins include Twin to Twin Transfusion Syndrome (TTTS) with the important topics screening, prognosis, complications of laser therapy, timing of delivery, risks for brain abnormalities and delayed neurological development, Twin Anemia-Polycythemia Sequence (TAPS) and Twin Reversed Arterial Perfusion (TRAP) Sequence. This also includes MC MA twins as well as conjoined twins.Finally, the birth mode and time for DC and MC twin pregnancies are described.The information is summarized in 62 recommendations for action, 4 tables and 8 illustrations with comprehensive background texts.The guideline is an international guideline adaptation (ISUOG, NICE) as well as a systematic literature search and is up-to-date. = In der folgenden AWMF-Leitlinie (DGGG/AGG & DEGUM federführend) werden die Diagnostik, das Screening und Management von Zwillingen sowie Zeitpunkt und Modus der Geburt behandelt.Zwillingsschwangerschaften können in dichorial-diamniale (DC DA), monochorial-diamniale (MC DA) und monoamniale (MC MA) – welche immer monochorial sind – unterteilt werden.Zwillingsschwangerschaften können für Chromosomenstörungen, Fehlbildungen, Wachstumsretardierung und hämodynamische Störungen konkordant (beide sind betroffen) oder diskordant sein (hier ist nur einer von beiden betroffen).Der prognostisch bedeutsamste Parameter ist die Chorionizität. Monochoriale Zwillinge weisen deutlich höhere Risiken für eine intrauterine Morbidität und Mortalität auf als dichoriale Zwillinge.Im Einzelnen wird Allgemeines zu Zwillingsschwangerschaften wie Datierung, Bestimmung der Chorionizität und Amnionizität, die Bezeichnung von Zwillingsfeten und das perinatale Switch-Phänomen diskutiert.Das Routine-Monitoring von MC- und DC-Zwillingsschwangerschaften mit Ultraschall zwischen 11 und 13+ 6 Schwangerschaftswochen auf Chromosomenstörungen, die invasive Pränataldiagnostik, Diskordanzen der NT oder SSL im ersten Trimenon, die frühe strukturierte Fehlbildungsdiagnostik sowie das Management bei für fetale Fehlbildungen diskordanten Zwillingen einschließlich des selektiven Fetozids werden beschrieben.Das Zweittrimester-Screening und Management auf Frühgeburt und auf intrauterine selektive Wachstumsrestriktion (sFGR), die Klassifikation monochorialer Zwillinge mit sFGR und das Management des überlebenden Zwillings nach Fruchttod des Co-Zwillings werden behandelt.Ausschließlich MC-Zwillinge betreffende Komplikationen sind das Zwillingstransfusionssyndrom (TTTS) mit den wichtigen Themen Screening, Prognose, Komplikationen der Lasertherapie, Entbindungszeitpunkt, Risiken für Gehirnanomalien und neurologische Entwicklungsverzögerung, die Twin Anemia–Polycythemia Sequence (TAPS) und die Twin Reversed Arterial Perfusion (TRAP) Sequence. Hierzu gehören auch die MC-MA-Zwillinge einschließlich der siamesischen Zwillinge.Zuletzt werden der Geburtsmodus und -zeitpunkt von DC- und MC-Zwillingsschwangerschaften beschrieben.Die Informationen sind in 62 Handlungsempfehlungen, 4 Tabellen und 8 Abbildungen mit umfassenden Hintergrundtexten zusammengefasst.Die Leitlinie ist eine internationale LL-Adaptation (ISUOG, NICE) sowie eine systematische Literaturrecherche und ist up to date