Impact of restrictive platelet transfusion strategies on transfusion rates: A cohort study in very preterm infants.

BACKGROUND: Evidence supports a restrictive platelet transfusion threshold in preterm neonates. We aimed to describe the effect of implementing this threshold on transfusion rates. STUDY DESIGN AND METHODS: This retrospective observational cohort study included all very preterm infants (born <32 weeks' gestation) admitted to a neonatal intensive care unit between 2004 and 2022, divided into three epochs. Platelet transfusion thresholds changed from 30 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2004 to December 2009) to 20 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2010 to June 2019) to 25 × 109/L for non-bleeding neonates and 50 × 109/L for neonates with major bleeding (July 2019 to July 2022). The primary outcome was the percentage of transfused neonates in each epoch. Secondary outcomes included the median number of transfusions per neonate, the percentage of transfusions given above 25 or 50 × 109/L, and major bleeding and mortality rates. RESULTS: The percentage of neonates transfused was 12.2% (115/939), 5.8% (96/1660), and 4.8% (25/525) in Epoch I, II, and III, respectively (p < .001), a relative reduction of 61%. The median number of transfusions per transfused neonate was 2.0 (interquartile range [IQR]: 1.0-3.0) in Epoch I, and 1.0 (IQR: 1.0-2.0) in subsequent Epochs (p = .04). The percentage of infants receiving at least one transfusion above 50 × 109/L in Epoch I, II, and III was 51.3% (59/115), 17.7% (17/96), and 20.0% (5/25; p < .001). Mortality and bleeding rates did not significantly differ between epochs. DISCUSSION: Implementation of restrictive platelet guidelines led to reduction of the rate and number of platelet transfusions.

Fetal and neonatal neuroimaging in twin-twin transfusion syndrome.

OBJECTIVES: To describe the types of brain injury and subsequent neurodevelopmental outcome in fetuses and neonates from pregnancies with twin-twin transfusion syndrome (TTTS). Additionally, to determine risk factors for brain injury and to review the use of neuroimaging modalities in these cases. METHODS: This was a retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. The primary outcome was the incidence of brain injury, classified into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment), risk factors for brain injury and the number of magnetic resonance imaging (MRI) scans. RESULTS: Cranial ultrasound was performed in all 466 TTTS pregnancies and in 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. Among those with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow-up was available for 29/34 (85%) long-term survivors with brain injury and the mean age at follow-up was 46 months. Neurodevelopmental impairment was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post-laser twin anemia-polycythemia sequence (TAPS) (odds ratio (OR), 3.095 (95% CI, 1.581-6.059); P = 0.001) and lower gestational age at birth (OR per 1-week decrease in gestational age, 1.381 (95% CI, 1.238-1.541); P < 0.001). CONCLUSIONS: Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post-laser TAPS and a lower gestational age at birth. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study.

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcome after selective fetal reduction in monochorionic twin pregnancies: A comparison of techniques over a 20-year period.

OBJECTIVE: To assess the perinatal outcome after fetal reduction in complicated monochorionic (MC) twin pregnancies by comparing different techniques. METHODS: A retrospective cohort study at a national referral center comparing data between four techniques: interstitial laser coagulation, radiofrequency ablation (RFA), fetoscopic laser coagulation (FLC) and bipolar cord coagulation (BCC). The primary outcome was the mortality of the co-twins. Secondary outcomes were preterm pre-labor rupture of membranes (PPROM), gestational age at delivery and neonatal morbidity. RESULTS: 259 MC twin pregnancies underwent selective fetal reduction: 29 IL, 64 RFA, 85 FLC and 81 BCC. The perinatal mortality rate was 29% and fetal demise of the co-twins occurred in 19%. The lowest mortality rate was seen after BCC (17%, p = 0.012). PPROM occurred in 18% patients without significant differences between techniques. The mean gestational age at delivery in liveborn children was 35 weeks and did not differ between techniques. Severe cerebral injury and neonatal morbidity were reported in 4% and 14%, respectively, without significant differences between techniques. CONCLUSIONS: Selective fetal reductions in MC twins are precarious procedures with an increased risk of perinatal mortality of the co-twins. Our results show the lowest mortality rates after BCC. However, high PPROM rates were seen irrespective of the technique.

Targeting neonatal Fc receptor: potential clinical applications in pregnancy.

The neonatal Fc receptor (FcRn) plays an important role in the transfer of the immunoglobulin G isotype (IgG) from the mother to the fetus. FcRn expressed on endothelial cells also binds to IgG and albumin, regulating the circulating half-lives of these proteins. Alloimmune and autoimmune IgG antibodies have been implicated in various perinatal immune-mediated diseases. FcRn-mediated placental transfer of pathogenic antibodies can result in cell and tissue injury in the fetus and neonate, with devastating outcomes. Thus, blockade of FcRn may be an effective treatment strategy in managing these conditions and could additionally reduce the concentration of pathogenic antibodies in the maternal circulation by preventing IgG recycling. In this review, we discuss the biology of FcRn, the rationale and considerations for development of FcRn-blocking agents, and their potential clinical applications in various perinatal immune-mediated diseases. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of fetal death in monochorionic twin pregnancies complicated by Type-III selective fetal growth restriction.

OBJECTIVE: Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify predictors of fetal death in these pregnancies. METHODS: This was an international multicenter retrospective cohort study. Type-III sFGR was defined as fetal estimated fetal weight (EFW) of one twin below the 10th percentile and intertwin EFW discordance of ≥ 25% in combination with intermittent absent or reversed end-diastolic flow in the umbilical artery of the smaller fetus. Predictors of fetal death were recorded longitudinally throughout gestation and assessed in univariable and multivariable logistic regression models. The classification and regression trees (CART) method was used to construct a prediction model of fetal death using significant predictors derived from the univariable analysis. RESULTS: A total of 308 twin pregnancies (616 fetuses) were included in the analysis. In 273 (88.6%) pregnancies, both twins were liveborn, whereas 35 pregnancies had single (n = 19 (6.2%)) or double (n = 16 (5.2%)) fetal death. On univariable analysis, earlier gestational age at diagnosis of Type-III sFGR, oligohydramnios in the smaller twin and deterioration in umbilical artery Doppler flow were associated with an increased risk of fetal death, as was larger fetal EFW discordance, particularly between 24 and 32 weeks' gestation. None of the parameters identified on univariable analysis maintained statistical significance on multivariable analysis. The CART model allowed us to identify three risk groups: a low-risk group (6.8% risk of fetal death), in which umbilical artery Doppler did not deteriorate; an intermediate-risk group (16.3% risk of fetal death), in which umbilical artery Doppler deteriorated but the diagnosis of sFGR was made at or after 16 + 5 weeks' gestation; and a high-risk group (58.3% risk of fetal death), in which umbilical artery Doppler deteriorated and gestational age at diagnosis was < 16 + 5 weeks' gestation. CONCLUSIONS: Type-III sFGR is associated with a high risk of fetal death. A prediction algorithm can help to identify the highest-risk group, which is characterized by Doppler deterioration and early referral. Further studies should investigate the potential benefit of fetal surveillance and intervention in this cohort. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Changes in structural brain development after selective fetal growth restriction in monochorionic twins.

OBJECTIVES: Fetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question, FGR singletons have been compared primarily to matched appropriately grown singletons, a design which is inherently biased by differences in genetic and maternal factors. To overcome these limitations, we conducted a within-pair comparison of neonatal structural cerebral ultrasound measurements in monochorionic twin pairs with selective FGR (sFGR). METHODS: Structural cerebral measurements on neonatal cerebral ultrasound were compared between the smaller and larger twins of monochorionic twin pairs with sFGR, defined as a birth-weight discordance (BWD) ≥ 20%, born in our center between 2010 and 2020. Measurements from each twin pair were also compared with those of an appropriately grown singleton, matched according to sex and gestational age at birth. RESULTS: Included were 58 twin pairs with sFGR, with a median gestational age at birth of 31.7 (interquartile range, 29.9-33.8) weeks and a median birth weight of 1155 g for the smaller twin and 1725 g for the larger twin (median BWD, 32%). Compared with both the larger twin and the singleton, the smaller twin had significantly smaller cerebral structures (corpus callosum, vermis, cerebellum), less white/deep gray matter and smaller intracranial surface area and volume. Intracranial-volume discordance and BWD correlated significantly (R2 = 0.228, P < 0.0001). The median intracranial-volume discordance was smaller than the median BWD (19% vs 32%, P < 0.0001). After correction for intracranial volume, only one of the observed differences (biparietal diameter) remained significant for the smaller twin vs both the larger twin and the singleton. CONCLUSIONS: In monochorionic twins with sFGR, neonatal cerebral ultrasound reveals an overall, proportional restriction in brain growth, with smaller cerebral structures, less white/deep gray matter and smaller overall brain-size parameters in the smaller twin. There was a positive linear relationship between BWD and intracranial-volume discordance, with intracranial-volume discordance being smaller than BWD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction.

OBJECTIVE: Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. METHODS: We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade > I, retinopathy of prematurity Stage > II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. RESULTS: We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n = 18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). CONCLUSIONS: In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence of placental dichotomy, fetal cardiomegaly and starry-sky liver in twin anemia-polycythemia sequence.

OBJECTIVE: To investigate the prevalence of three additional ultrasound markers, placental dichotomy, cardiomegaly and 'starry-sky' liver, in monochorionic twin pregnancy with twin anemia-polycythemia sequence (TAPS). METHODS: All monochorionic twin pregnancies, diagnosed antenatally with TAPS at our center between 2006 and 2019, were reviewed retrospectively for the presence of placental dichotomy, cardiomegaly in the donor twin and a starry-sky liver in the recipient twin. TAPS was diagnosed based on delta middle cerebral artery (MCA) peak systolic velocity (PSV) > 0.5 multiples of the median. The primary outcome was the prevalence of placental dichotomy, cardiomegaly, starry-sky liver and at least one of these markers in both spontaneous and post-laser TAPS. The secondary outcome was the prevalence of these ultrasound markers according to the antenatal stage of TAPS. RESULTS: A total of 91 monochorionic twin pregnancies with TAPS were eligible for analysis. Placental dichotomy was observed in 44% (40/91) of TAPS cases. A total of 70% (64/91) of the TAPS donors developed cardiomegaly and a starry-sky liver was identified in 66% (53/80) of the TAPS recipients. The prevalence of cardiomegaly and starry-sky liver was roughly comparable between spontaneous and post-laser TAPS (69% (33/48) vs 72% (31/43) and 64% (25/39) vs 68% (28/41), respectively). Pregnancies with spontaneous TAPS showed a higher prevalence of placental dichotomy compared with post-laser TAPS (63% (30/48) vs 23% (10/43)). At least one of the three ultrasound markers was detected in 86% (78/91) of TAPS cases, meaning that 14% (13/91) of cases presented solely with discordant MCA-PSV values. There was a trend towards increased prevalence of all three ultrasound markers with increasing antenatal TAPS stage. CONCLUSIONS: Placental dichotomy, fetal cardiomegaly and a starry-sky liver are commonly found in TAPS pregnancy. Investigating the presence of these ultrasound markers can be of additional help in improving antenatal detection of TAPS in monochorionic twin pregnancy. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Consensus diagnostic criteria and monitoring of twin anemia-polycythemia sequence: Delphi procedure.

OBJECTIVES: Twin anemia-polycythemia sequence (TAPS) is associated with increased perinatal morbidity and mortality. Inconsistencies in the diagnostic criteria for TAPS exist, which hinder the ability to establish robust evidence-based management or monitoring protocols. The main aim of this study was to determine, by expert consensus using a Delphi procedure, the key diagnostic features and optimal monitoring approach for TAPS. METHODS: A Delphi process was conducted among an international panel of experts on TAPS. Panel members were provided with a list of literature-based parameters for diagnosing and monitoring TAPS. They were asked to rate the importance of the parameters on a five-point Likert scale. Consensus was sought to determine the cut-off values for accepted parameters, as well as parameters used in the monitoring of and assessment of outcome in twin pregnancy complicated by TAPS. RESULTS: A total of 132 experts were approached. Fifty experts joined the first round, of whom 33 (66%) completed all three rounds. There was agreement that the monitoring interval for the development of TAPS should be every 2 weeks and that the severity should be assessed antenatally using a classification system based on middle cerebral artery (MCA) peak systolic velocity (PSV), but there was no agreement on the gestational age at which to start monitoring. Once the diagnosis of TAPS is made, monitoring should be scheduled weekly. For the antenatal diagnosis of TAPS, the combination of MCA-PSV ≥ 1.5 MoM in the anemic twin and ≤ 0.8 MoM in the polycythemic twin was agreed. Alternatively, MCA-PSV discordance ≥ 1 MoM can be used to diagnose TAPS. Postnatally, hemoglobin difference ≥ 8 g/dL and intertwin reticulocyte ratio ≥ 1.7 were agreed criteria for diagnosis of TAPS. There was no agreement on the cut-off of MCA-PSV or its discordance for prenatal intervention. The panel agreed on prioritizing perinatal and long-term survival outcomes in follow-up studies. CONCLUSIONS: Consensus-based diagnostic features of TAPS, as well as cut-off values for the parameters involved, were agreed upon by a panel of experts. Future studies are needed to validate these diagnostic features before they can be used in clinical trials of interventions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Treatment and outcome of 370 cases with spontaneous or post-laser twin anemia-polycythemia sequence managed in 17 fetal therapy centers.

OBJECTIVE: To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post-laser twin anemia-polycythemia sequence (TAPS). METHODS: This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post-laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and < 1.0 MoM in the TAPS recipient. The following antenatal management groups were defined: expectant management, delivery within 7 days after diagnosis, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)), laser surgery and selective feticide. Cases were assigned to the management groups based on the first treatment that was received after diagnosis of TAPS. The primary outcomes were perinatal mortality and severe neonatal morbidity. The secondary outcome was diagnosis-to-birth interval. RESULTS: In total, 370 monochorionic twin pregnancies were diagnosed antenatally with TAPS during the study period and included in the study. Of these, 31% (n = 113) were managed expectantly, 30% (n = 110) with laser surgery, 19% (n = 70) with IUT (± PET), 12% (n = 43) with delivery, 8% (n = 30) with selective feticide and 1% (n = 4) underwent termination of pregnancy. Perinatal mortality occurred in 17% (39/225) of pregnancies in the expectant-management group, 18% (38/215) in the laser group, 18% (25/140) in the IUT (± PET) group, 10% (9/86) in the delivery group and in 7% (2/30) of the cotwins in the selective-feticide group. The incidence of severe neonatal morbidity was 49% (41/84) in the delivery group, 46% (56/122) in the IUT (± PET) group, 31% (60/193) in the expectant-management group, 31% (57/182) in the laser-surgery group and 25% (7/28) in the selective-feticide group. Median diagnosis-to-birth interval was longest after selective feticide (10.5 (interquartile range (IQR), 4.2-14.9) weeks), followed by laser surgery (9.7 (IQR, 6.6-12.7) weeks), expectant management (7.8 (IQR, 3.8-14.4) weeks), IUT (± PET) (4.0 (IQR, 2.0-6.9) weeks) and delivery (0.3 (IQR, 0.0-0.5) weeks). Treatment choice for TAPS varied greatly within and between the 17 fetal therapy centers. CONCLUSIONS: Antenatal treatment for TAPS differs considerably amongst fetal therapy centers. Perinatal mortality and morbidity were high in all management groups. Prolongation of pregnancy was best achieved by expectant management, treatment by laser surgery or selective feticide. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

High risk of long-term neurodevelopmental impairment in donor twins with spontaneous twin anemia-polycythemia sequence.

OBJECTIVES: To evaluate the long-term neurodevelopmental and behavioral outcomes in surviving infants of pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS), to compare outcome between donors and recipients, and to investigate potential risk factors for neurodevelopmental impairment (NDI). METHODS: This was a retrospective study of a consecutive cohort of spontaneous-TAPS survivors delivered between 2005 and 2017 at the Leiden University Medical Center, The Netherlands. Neurological, motor, cognitive and behavioral development were assessed at a median age of 4 years. The primary outcome was NDI, which was a composite outcome of cerebral palsy, deafness, blindness and motor and/or cognitive delay. NDI was subdivided into two grades of severity: mild-to-moderate and severe NDI. Outcome was compared between surviving donor and recipient twins. Logistic regression analysis was used to assess risk factors for NDI. RESULTS: Forty-nine twin pregnancies complicated by spontaneous TAPS were eligible for inclusion. The perinatal survival rate was 83% (81/98) of twins. Neurodevelopmental assessment was performed in 91% (74/81) of surviving twins. NDI occurred in 30% (22/74) of TAPS survivors, and was found more often in donors (44%; 15/34) than in recipients (18%; 7/40) (odds ratio (OR), 4.1; 95% CI, 1.8-9.1; P = 0.001). Severe NDI was detected in 9% (7/74) of survivors and was higher in donors compared with recipients (18% (6/34) vs 3% (1/40)), although the difference did not reach statistical significance; P = 0.056). Donors demonstrated lower cognitive scores compared with recipients (P = 0.011). Bilateral deafness was identified in 15% (5/34) of donors compared with 0% (0/40) of recipients (P = 0.056). Parental concern regarding development was reported more often for donor than for recipient twins (P = 0.001). On multivariate analysis, independent risk factors for NDI were gestational age at delivery (OR, 0.7; 95% CI, 0.5-0.9; P = 0.003) and severe anemia (OR, 6.4; 95% CI, 2.4-17.0; P < 0.001). CONCLUSION: Surviving donor twins of pregnancies complicated by spontaneous TAPS have four-fold higher odds of NDI compared with recipient cotwins, are at increased risk of cognitive delay and have a high rate of deafness. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Core outcome set for studies investigating management of selective fetal growth restriction in twins.

OBJECTIVE: Selective fetal growth restriction (sFGR) occurs in monochorionic twin pregnancies when unequal placental sharing leads to restriction in the growth of just one twin. Management options include laser separation of the fetal circulations, selective reduction or expectant management, but what constitutes the best treatment is not yet known. New trials in this area are urgently needed but, in this rare and complex group, maximizing the relevance and utility of clinical research design and outputs is paramount. A core outcome set ensures standardized outcome collection and reporting in future research. The objective of this study was to develop a core outcome set for studies evaluating treatments for sFGR in monochorionic twins. METHODS: An international steering group of clinicians, researchers and patients with experience of sFGR was established to oversee the process of development of a core outcome set for studies investigating the management of sFGR. Outcomes reported in the literature were identified through a systematic review and informed the design of a three-round Delphi survey. Clinicians, researchers, and patients and family representatives participated in the survey. Outcomes were scored on a Likert scale from 1 (limited importance for making a decision) to 9 (critical for making a decision). Consensus was defined a priori as a Likert score of ≥ 8 in the third round of the Delphi survey. Participants were then invited to take part in an international meeting of stakeholders in which the modified nominal group technique was used to consider the consensus outcomes and agree on a final core outcome set. RESULTS: Ninety-six outcomes were identified from 39 studies in the systematic review. One hundred and three participants from 23 countries completed the first round of the Delphi survey, of whom 88 completed all three rounds. Twenty-nine outcomes met the a priori criteria for consensus and, along with six additional outcomes, were prioritized in a consensus development meeting, using the modified nominal group technique. Twenty-five stakeholders participated in this meeting, including researchers (n = 3), fetal medicine specialists (n = 3), obstetricians (n = 2), neonatologists (n = 3), midwives (n = 4), parents and family members (n = 6), patient group representatives (n = 3), and a sonographer. Eleven core outcomes were agreed upon. These were live birth, gestational age at birth, birth weight, intertwin birth-weight discordance, death of surviving twin after death of cotwin, loss during pregnancy or before final hospital discharge, parental stress, procedure-related adverse maternal outcome, length of neonatal stay in hospital, neurological abnormality on postnatal imaging and childhood disability. CONCLUSIONS: This core outcome set for studies investigating the management of sFGR represents the consensus of a large and diverse group of international collaborators. Use of these outcomes in future trials should help to increase the clinical relevance of research on this condition. Consensus agreement on core outcome definitions and measures is now required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Outcome of twin-to-twin transfusion syndrome in monochorionic monoamniotic twin pregnancy: systematic review and meta-analysis.

OBJECTIVES: To explore the outcome of monochorionic monoamniotic (MCMA) twin pregnancies affected by twin-to-twin transfusion syndrome (TTTS). METHODS: MEDLINE and EMBASE databases were searched for studies reporting the outcome of MCMA twin pregnancies complicated by TTTS. The primary outcome was intrauterine death (IUD); secondary outcomes were miscarriage, single IUD, double IUD, neonatal death (NND), perinatal death (PND), survival of at least one twin, survival of both twins and preterm birth (PTB) before 32 weeks' gestation. Outcomes were assessed in MCMA twins affected by TTTS not undergoing intervention and in those treated with amniodrainage, laser therapy or cord occlusion. Subgroup analysis was performed including cases diagnosed before 24 weeks. Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Fifteen cohort studies, including 888 MCMA twin pregnancies, of which 44 were affected by TTTS, were included in the review. There was no randomized trial comparing the different management options in MCMA twin pregnancies complicated by TTTS. In cases not undergoing intervention, miscarriage occurred in 11.0% of fetuses, while the incidence of IUD, NND and PND was 25.2%, 12.2% and 31.2%, respectively. PTB complicated 50.5% of these pregnancies. In cases treated by laser surgery, the incidence of miscarriage, IUD, NND and PND was 19.6%, 27.4%, 7.4% and 35.9%, respectively, and the incidence of PTB before 32 weeks' gestation was 64.9%. In cases treated with amniodrainage, the incidence of IUD, NND and PND was 31.3%, 13.5% and 45.7% respectively, and PTB complicated 76.2% of these pregnancies. Analysis of cases undergoing cord occlusion was affected by the very small number of included cases. Miscarriage occurred in 19.2%, while there was no case of IUD or NND of the surviving twin. PTB before 32 weeks occurred in 50.0% of these cases. CONCLUSIONS: MCMA twin pregnancies complicated by TTTS are at high risk of perinatal mortality and PTB. Further studies are needed in order to elucidate the optimal type of prenatal treatment in these pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12-18 weeks gestational age using high dosage and in standard-risk FNAIT at 20-28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.

Improved prediction of twin anemia-polycythemia sequence by delta middle cerebral artery peak systolic velocity: new antenatal classification system.

OBJECTIVES: To investigate the diagnostic accuracy of delta middle cerebral artery peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) and compare its predictive value with that of the current MCA-PSV cut-off values of > 1.5 MoM in the donor and < 1.0 MoM in the recipient, for the diagnosis of twin anemia-polycythemia sequence (TAPS) in monochorionic twin pregnancy. METHODS: This was a retrospective consecutive cohort study comprising all uncomplicated monochorionic twin pregnancies and twin pregnancies with a postnatal diagnosis of TAPS managed between 2003 and 2017 in the Dutch national referral center for fetal therapy. Cases with incomplete MCA-PSV Doppler measurements 1 week prior to delivery or with incomplete hemoglobin measurements within 1 day after birth were excluded. The postnatal diagnosis of TAPS was based on an intertwin hemoglobin difference > 8 g/dL and at least one of the following: reticulocyte count ratio > 1.7 or presence of minuscule anastomoses on the placental surface. We compared the predictive accuracy of the current diagnostic method using MCA-PSV cut-off values of > 1.5 MoM in the donor and < 1.0 MoM in the recipient with that of a new method based on intertwin difference in MCA-PSV > 0.5 MoM for prediction of TAPS. RESULTS: In total, 45 uncomplicated and 35 TAPS monochorionic twin pregnancies were analyzed. The sensitivity and specificity of the cut-off MCA-PSV values (donor > 1.5 MoM, recipient < 1.0 MoM) to predict TAPS was 46% (95% CI, 30-62%) and 100% (95% CI, 92-100%), respectively; positive predictive value was 100% (95% CI, 81-100%) and negative predictive value 70% (95% CI, 58-80%). Delta MCA-PSV showed a sensitivity of 83% (95% CI, 67-92%) and a specificity of 100% (95% CI, 92-100%); the positive and negative predictive values were 100% (95% CI, 88-100%) and 88% (95% CI, 77-94%), respectively. Of the 35 cases with TAPS diagnosed postnatally, 13 twin pairs showed a delta MCA-PSV > 0.5 MoM but did not fulfill the cut-off MCA-PSV criteria. Of these 13 TAPS twins, nine donors and four recipients had normal MCA-PSV values. There was a high correlation between delta MCA-PSV and intertwin difference in hemoglobin level (R = 0.725, P < 0.01). CONCLUSION: Delta MCA-PSV > 0.5 MoM has a greater diagnostic accuracy for predicting TAPS compared to the current MCA-PSV cut-off criteria. We therefore propose a new antenatal classification system for TAPS. In monochorionic twin pregnancies with delta MCA-PSV > 0.5 MoM on Doppler ultrasound, but normal MCA-PSV values in the donor or recipient, obstetricians should be aware of the therapeutic implications and neonatal morbidities associated with TAPS. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Core outcome set for research studies evaluating treatments for twin-twin transfusion syndrome.

OBJECTIVE: To develop, using a Delphi procedure and a nominal group technique, a core outcome set (COS) for studies evaluating treatments for twin-twin transfusion syndrome (TTTS), which should assist in standardizing outcome selection, collection and reporting in future research studies. METHODS: An international steering group comprising healthcare professionals, researchers and patients with experience of TTTS guided the development of this COS. Potential core outcomes, identified through a comprehensive literature review and supplemented by outcomes suggested by the steering group, were entered into a three-round Delphi survey. Healthcare professionals, researchers, and patients or relatives of patients who had experienced TTTS were invited to participate. Consensus was defined a priori using the 15%/70% definition of the Core Outcome Measures in Effectiveness Trials (COMET) initiative. The modified nominal group technique was used to evaluate the consensus outcomes in a face-to-face consultation meeting and identify the final COS. RESULTS: One hundred and three participants, from 29 countries, participated in the three-round Delphi survey. Of those, 88 completed all three rounds. Twenty-two consensus outcomes were identified through the Delphi procedure and entered into the modified nominal group technique. The consensus meeting was attended by 11 healthcare professionals, two researchers and three patients; 12 core outcomes were prioritized for inclusion in the COS. Fetal core outcomes included live birth, pregnancy loss (including miscarriage, stillbirth, termination of pregnancy and neonatal mortality), subsequent death of a cotwin following single-twin demise at the time of treatment, recurrence of TTTS, twin anemia-polycythemia sequence and amniotic band syndrome. Neonatal core outcomes included gestational age at delivery, birth weight, brain injury syndromes and ischemic limb injury. Maternal core outcomes included maternal mortality and admission to Level-2 or -3 care setting. One aspirational outcome, neurodevelopment at 18-24 months of age, was also prioritized. CONCLUSIONS: Implementing the COS for TTTS within future research studies could make a substantial contribution to advancing the usefulness of research in TTTS. Standardized definitions and measurement instruments are now required for individual core outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Incidence of and Risk Factors for Residual Anastomoses in Twin-Twin Transfusion Syndrome Treated with Laser Surgery: A 15-Year Single-Center Experience.

OBJECTIVES: To evaluate the incidence of residual anastomoses (RA) after laser therapy for twin-twin transfusion syndrome (TTS) and investigate risk factors for incomplete laser surgery. MATERIAL AND METHODS: All available TTS placentas treated with laser at our center between 2002 and 2016 were injected with color dye to assess the presence of RA. We evaluated the incidence of RA over the past 15 years by dividing the cohort into three time periods, and studied the association with risk factors and neonatal outcome. RESULTS: Overall, RA were detected in 21.0% (78/371) of placentas. The incidence of RA decreased from 38.8% (26/67) in the initial period to 11.7% (16/137) in the most recent period (p < 0.001). On multivariate analysis, several risk factors were independently associated with the risk of RA, including Solomon laser technique (odds ratio [OR] 0.17, 95% CI 0.09-0.33) and estimation of surgical success (OR 19.28, 95% CI 8.17-45.49). Premature delivery and neonatal morbidity occurred more often in TTS cases with RA. CONCLUSIONS: The incidence of RA after laser therapy for TTS decreased significantly in the past 15 years and is now below 15% due to the use of the Solomon technique.

Impact of cannula size on recurrent twin-twin transfusion syndrome and twin anemia-polycythemia sequence after fetoscopic laser surgery.

OBJECTIVE: The optimal outcome after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) depends on the successful ablation of all placental anastomoses. The objective of this study was to determine the incidence of and risk factors for recurrent TTTS (rTTTS) or twin anemia-polycythemia sequence (TAPS) after FLS, focusing on the impact of cannula diameter. METHODS: This was a secondary analysis of data collected prospectively at two centers from 666 consecutive patients undergoing FLS for TTTS. The main outcomes were rTTTS and TAPS following FLS. Variables assessed included gestational age at intervention, stage of disease, recipient maximum vertical pocket, anterior placenta, number of anastomoses ablated, cannula diameter/operative scopes and use of the Solomon technique. Cannula diameter and corresponding scopes used were as follows: 8 Fr and 1.3 mm/0°; 9 Fr and 2.7 mm/0°; 10 Fr and 3 mm/0°; or 12 Fr and 3.3-3.7 mm/30-70°. Cannula diameter was used as a surrogate for scopes during analysis. Multivariate logistic regression analysis was performed to identify risk factors associated with rTTTS or TAPS after FLS; 'center' was considered an independent variable to account for variations in practice. In a nested cohort of pregnancies in which both fetuses survived, placental dye injection was performed in 315 placentae. Multivariate logistic regression analysis was performed to evaluate variables associated with the presence of residual anastomoses. RESULTS: rTTTS or TAPS occurred in 61 (9%) cases following FLS (rTTTS in eight (1%) and TAPS in 53 (8%)). Factors associated significantly with the risk of rTTTS/TAPS on multivariate analysis were cannula diameter (when an 8-Fr, 9-Fr, 10-Fr or 12-Fr cannula was used, there was rTTTS/TAPS in 24%, 13%, 2% or 0.8% of cases, respectively (P < 0.001)) and use of the Solomon technique (rTTTS/TAPS occurred in 4.2% of those in which it was used vs 18.1% in those in which it was not (P < 0.001)). Only use of the Solomon technique was associated significantly with no residual anastomoses found after delivery. CONCLUSIONS: Following FLS for TTTS, a lower incidence of rTTTS/TAPS was seen when the Solomon technique was used, as well as when a 10-Fr or 12-Fr cannula was used. A lower complication rate may be due to the use of a scope with better optics during placental mapping. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.