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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. [ABSTRACT FROM AUTHOR]

The article considers the benefits of contingent screening against primary screening by cell-free DNA testing. Topics discussed include non-invasive prenatal testing (NIPT) via cell-free DNA analysis, NIPT implementation in public-health-based programs, and the lack of evidence for additional perceived benefits of serum screening or nuchal translucency (NT) measurement.

The article presents the author's views on the non-invasive prenatal testing (NIPT) for pregnant women who want to detect trisomy 21 in their unborn child. It states that NIPT improve the quality of prenatal testing for fetal abnormalities. It further discusses aneuploidy screening, chromosomal microarray analysis and testing in pregnancy.

Objective To describe the outcome of pregnancies with fetal and neonatal alloimmune thrombocytopenia (FNAIT) in relation to the invasiveness of the management protocol. Design Retrospective analysis of prospectively collected data from a national cohort. Setting Leiden University Medical Centre, the national centre for management of severe red cell and platelet alloimmunisation in pregnancy. Population Ninety-eight pregnancies in 85 women with FNAIT having a previous child with thrombocytopenia with ( n= 16) or without ( n= 82) an intracranial haemorrhage (ICH). Methods Our management protocol evolved over time from (1) serial fetal blood samplings (FBS) and platelet transfusion ( n= 13) via (2) combined FBS with maternal intravenous immunoglobulins ( n= 33) to (3) completely noninvasive treatment with immunoglobulins only ( n= 52 pregnancies, resulting in 53 neonates). Perinatal outcome was assessed according to the three types of management. Main outcome measures Occurrence of ICH, perinatal survival, gestational age at birth and complications of FBS. Results All but one of 98 pregnancies ended in a live birth; none of the neonates had an ICH. The median gestational age at birth was 37 weeks (range 32–40). In groups 1 and 2, three emergency caesarean sections were performed after complicated FBS, resulting in two healthy babies and one neonatal death. Conclusion Noninvasive antenatal management of pregnancies complicated by FNAIT appears to be both effective and safe. [ABSTRACT FROM AUTHOR]

Background: Pregnancies complicated by Rh alloimmunization have been evaluated with the use of serial invasive amniocentesis to determine bilirubin levels by measuring in the amniotic fluid the change in optical density at a wavelength of 450 nm (DeltaOD450); however, this procedure carries risks. Noninvasive Doppler ultrasonographic measurement of the peak velocity of systolic blood flow in the middle cerebral artery also predicts severe fetal anemia, but this test has not been rigorously evaluated in comparison with amniotic-fluid DeltaOD450.Methods: We performed a prospective, international, multicenter study including women with RhD-, Rhc-, RhE-, or Fy(a)-alloimmunized pregnancies with indirect antiglobulin titers of at least 1:64 and antigen-positive fetuses to assess whether Doppler ultrasonographic measurement of the peak systolic velocity of blood flow in the middle cerebral artery was at least as sensitive and accurate as measurement of amniotic-fluid DeltaOD450 for diagnosing severe fetal anemia. The results of the two tests were compared with the incidence of fetal anemia, as determined by measurement of hemoglobin levels in fetal blood.Results: Of 165 fetuses, 74 had severe anemia. For the detection of severe fetal anemia, Doppler ultrasonography of the middle cerebral artery had a sensitivity of 88 percent (95 percent confidence interval, 78 to 93 percent), a specificity of 82 percent (95 percent confidence interval, 73 to 89 percent), and an accuracy of 85 percent (95 percent confidence interval, 79 to 90 percent). Amniotic-fluid DeltaOD450 had a sensitivity of 76 percent (95 percent confidence interval, 65 to 84 percent), a specificity of 77 percent (95 percent confidence interval, 67 to 84 percent), and an accuracy of 76 percent (95 percent confidence interval, 69 to 82 percent). Doppler ultrasonography was more sensitive, by 12 percentage points (95 percent confidence interval, 0.3 to 24.0), and more accurate, by 9 percentage points (95 percent confidence interval, 1.1 to 15.9), than measurement of amniotic-fluid DeltaOD450.Conclusions: Doppler measurement of the peak velocity of systolic blood flow in the middle cerebral artery can safely replace invasive testing in the management of Rh-alloimmunized pregnancies. (ClinicalTrials.gov number, NCT00295516.). [ABSTRACT FROM AUTHOR]

Abstract Objective Learning curves pose a difficult problem in the teaching of technical skills: how do you teach procedural skills without compromising patients’ health? A simulator-based curriculum has been designed to minimize the risks to patients undergoing amniocentesis by shifting the learning curve away from patients and into the laboratory. This study evaluated the effectiveness of a high-fidelity simulator-based curriculum in improving the performance of amniocentesis by obstetric trainees. Design Thirty trainees received a course on the practice of amniocentesis. The curriculum consisted of a lecture, a syllabus, and a hands-on training session with the simulator. Pre- and post-training performance were evaluated with two rating scales. Training and performance evaluation were completed using the same simulator. The effectiveness of the simulator-based workshop and the effect of year of training were assessed using a two-way analysis of variance. Results Performance scores improved from a mean score of 55% to 94% using checklist scoring and from 57% to 88% using global ratings. The two-way analysis of variance revealed a significant effect of training (F1,60 = 43.57; P < 0.001) accounting for 45% of the variance in scores, and a significant effect of experience level (F2,60 = 9.16; P < 0.001) accounting for 25% of the variance in scores. Conclusions A comprehensive curriculum based on a high-fidelity simulator was effective at improving skills demonstrated on the simulator. The challenge remains to establish that skills acquired on a simulator are transferable to the clinical setting. [ABSTRACT FROM AUTHOR]

ABSTRACTObjectivesTo evaluate the potential usefulness of noninvasive ultrasound assessment of fetal anemia in the diagnosis and management of fetuses with homozygous alpha-thalassemia-1. MethodsWe describe four pregnancies complicated by fetal homozygous alpha-thalassemia-1. They presented with ultrasound abnormalities before the development of hydrops. As part of evaluating the fetal condition, we performed ultrasound and Doppler studies aimed at identifying fetal anemia. These studies included evaluation of intrahepatic umbilical venous maximum flow velocity, middle cerebral artery peak flow velocity, fetal liver length and spleen perimeter. ResultsIn all four fetuses, ultrasound and Doppler studies suggested the presence of fetal anemia. Homozygous alpha-thalassemia-1 was diagnosed in all cases, with fetal blood sampling confirming anemia in three fetuses. The majority of the intrahepatic umbilical venous maximum flow velocity and middle cerebral artery peak flow velocity measurements were above the 95th centile. Two fetuses underwent intrauterine transfusion and fetal blood flow velocities returned to normal after correction of the fetal anemia. The fetal liver length and spleen perimeter measurements showed a similar trend, although they were less consistent before 28 weeks. ConclusionNon-invasive ultrasound parameters, in particular quantification of intrahepatic umbilical venous maximum flow velocity and middle cerebral artery peak flow velocity, were found to be useful in the diagnosis and management of fetal anemia in pregnancies with fetal homozygous alpha-thalassemia-1. [ABSTRACT FROM AUTHOR]

Linked Comment: Ultrasound Obstet Gynecol 2014:43:48–53 [ABSTRACT FROM AUTHOR]

Microcystic or solid-looking fetal lung lesions associated with hydrops are associated with a high mortality rate. The most common of these lesions are microcystic congenital cystic adenomatoid malformations and pulmonary sequestrations (PS). Performing open fetal surgery by hysterotomy and lobectomy has, until now, been the only therapeutic option available following diagnosis of these lesions in the second trimester. Here we describe a new minimally invasive technique for the treatment of PS in the second trimester. Laser coagulation of the feeding systemic artery of the sequestration was performed under ultrasound guidance. The blood flow to the lung tumor was successfully arrested and hydrops reversed. The child was born at term and, at the time of writing, was alive and well at 2 years of age. Large PS with hydrops can be treated successfully by ultrasound-guided minimally invasive laser surgery. It is therefore important to utilize color Doppler ultrasound imaging for identification of a systemic feeding blood vessel in solid fetal lung tumors. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the safety of vaginal delivery in pregnancies with fetal and neonatal alloimmune thrombocytopenia (FNAIT). Design Prospective data collection. Setting Leiden University Medical Centre, the national centre for management of severe red cell and platelet alloimmunisation. Population Thirty-two pregnancies with FNAIT, with a sibling with thrombocytopenia but without an intracranial haemorrhage (ICH). Methods The mode of delivery, platelet count in cord blood and neonatal outcome were analysed. All women received weekly intravenous immunoglobulin from 32 to 38 weeks of gestation. Head ultrasound scan was performed in all neonates. Main outcome measures Signs of ICH or other bleeding in the neonates. Results Twenty-three women delivered vaginally. Nine caesarean sections were performed, all for obstetric reasons. Median platelet count at birth was 142 × 109/l (range, 4–252 × 109/l), with severe thrombocytopenia (<50 ×109/l) in four neonates, of which three were born vaginally. None of the neonates showed signs of ICH or other bleeding. Conclusions In pregnancies with FNAIT and a thrombocytopenic sibling without ICH, vaginal delivery was not associated with neonatal intracranial bleeding. These initial results support our noninvasive management of these pregnancies with FNAIT. [ABSTRACT FROM AUTHOR]

The article focuses on the management of congenital high airway obstruction syndrome through ex-utero intrapartum treatment. The obstruction of the airways caused by factors such as dilated trachea and enlarged lungs should be addressed properly before it might lead to intrauterine fetal death. It has been found out that accurate prenatal diagnosis of the typical sonographic characteristics of the syndrome resulted to an effective ex-utero intrapartum tracheoplasty delivery.

An abstract of the article "Hypoplasia of abdominal muscles: a rare complication following fetal ascites due to maternofetal parvovirus B19 infection," by E. Jong-Pleij, D. Oepkes, and L. S. Ribbert is presented.

Objective: The perinatal outcomes in second-trimester abdominal circumference (AC) discordant twins are yet to be established. The aim of this study was to ascertain perinatal risks associated with second-trimester AC discordance in monochorionic (MC) twins. Method: We conducted a retrospective study of all MC twin pregnancies over a 7-year period. Intertwin AC discordance at 14–26 gestational weeks was analyzed in relation to Doppler abnormalities, obstetric complications, and perinatal adverse outcomes. Results: A total of 246 MC twin pregnancies were included in the analysis. The smaller twins of second-trimester AC discordant pairs were at increased prevalence of abnormal umbilical artery flow (50% versus 24%, p < .001) and low positive A wave of ductus venous flow (24% versus 9%, p = .002). The second-trimester AC discordant twins were at increased risk of oligohydramnios in smaller twin (OR = 2.44, 95% CI = 1.37–4.32, p < .01), cardiomegaly in larger twin (OR = 2.95, 95% CI = 1.01–8.60, p < .05), birth weight of either twin below the 10th percentile for gestational age (OR = 5.56, 95% CI = 2.67–11.59, p < .001), birth weight discordance > 25% (OR = 9.41, 95% CI = 4.46–19.87, p < .001), IUFD (OR = 3.26, 95% CI = 1.76–6.05, p < .001), and severe neonatal morbidity (OR = 1.83, 95% CI = 1.03–3.26, p < .05). The intact survival rate in discordant and concordant twin pairs was 70% and 89%, respectively (p < .001). Conclusions: Early and increase fetal surveillance of the second-trimester AC discordant twins should be utilized to establish perinatal risks, thus allowing prenatal care to improve. [ABSTRACT FROM AUTHOR]

Objective: The perinatal outcomes in second-trimester abdominal circumference (AC) discordant twins are yet to be established. The aim of this study was to ascertain perinatal risks associated with second-trimester AC discordance in monochorionic (MC) twins.Method: We conducted a retrospective study of all MC twin pregnancies over a 7-year period. Intertwin AC discordance at 14-26 gestational weeks was analyzed in relation to Doppler abnormalities, obstetric complications, and perinatal adverse outcomes.Results: A total of 246 MC twin pregnancies were included in the analysis. The smaller twins of second-trimester AC discordant pairs were at increased prevalence of abnormal umbilical artery flow (50% versus 24%, p < .001) and low positive A wave of ductus venous flow (24% versus 9%, p = .002). The second-trimester AC discordant twins were at increased risk of oligohydramnios in smaller twin (OR = 2.44, 95% CI = 1.37-4.32, p < .01), cardiomegaly in larger twin (OR = 2.95, 95% CI = 1.01-8.60, p < .05), birth weight of either twin below the 10th percentile for gestational age (OR = 5.56, 95% CI = 2.67-11.59, p < .001), birth weight discordance > 25% (OR = 9.41, 95% CI = 4.46-19.87, p < .001), IUFD (OR = 3.26, 95% CI = 1.76-6.05, p < .001), and severe neonatal morbidity (OR = 1.83, 95% CI = 1.03-3.26, p < .05). The intact survival rate in discordant and concordant twin pairs was 70% and 89%, respectively (p < .001).Conclusions: Early and increase fetal surveillance of the second-trimester AC discordant twins should be utilized to establish perinatal risks, thus allowing prenatal care to improve. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the outcome of fetoscopy and laser with an alternative technique in twin-to-twin transfusion syndrome (TTTS).

Presents a letter to the editor in response to the article "The Effect of the Term Breech Trial on Medical Intervention Behaviour and Neonatal Outcome in the Netherlands: An Analysis of 35,453 Term Breech Infants," by C.C. Rietberg, et al., in the 2005 issue of "BJOG: An International Journal of Obstetrics and Gynaecology."

Objective: To evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The second objective was assessment of the current prevalence of RhD immunisations. Design Prospective cohort study. Setting: The Netherlands. Population: Two‐year nationwide cohort of alloimmunised RhD‐negative women. Methods: RhD‐negative women in their first RhD immunised pregnancy were included for risk factor analysis. We compared risk factors for RhD immunisation, occurring either in the previous non‐immunised pregnancy or in the index pregnancy, with national population data derived from the Dutch perinatal registration (Perined). Results: In the 2‐year cohort, data from 193 women were eligible for analysis. Significant risk factors in women previously experiencing a pregnancy of an RhD‐positive child (n = 113) were: caesarean section (CS) (OR 1.7, 95% CI 1.1–2.6), perinatal death (OR 3.5, 95% CI 1.1–10.9), gestational age >42 weeks (OR 6.1, 95% CI 2.2–16.6), postnatal bleeding (>1000 ml) (OR 2.0, 95% CI 1.1–3.6), manual removal of the placenta (MRP) (OR 4.3, 95% CI 2.0–9.3); these factors often occurred in combination. The miscarriage rate was significantly higher than in the Dutch population (35% versus 12.‐5%, P < 0.001). Conclusion: Complicated deliveries, including cases of major bleeding and surgical interventions (CS, MRP), must be recognised as a risk factor, requiring estimation of fetomaternal haemorrhage volume and adjustment of RhIg dosing. The higher miscarriage rate suggests that existing RhIg protocols need adjustment or better compliance. Complicated delivery (caesarean section, manual removal placenta, major bleeding) is the most valid risk factor for RhD immunization despite antenatal and postnatal RhIg. Complicated delivery (caesarean section, manual removal placenta, major bleeding) is the most valid risk factor for RhD immunization despite antenatal and postnatal RhIg. [ABSTRACT FROM AUTHOR]

Background and Objectives Ferritin levels are often highly elevated at birth in neonates with alloimmune haemolytic disease of the fetus and newborn ( HDFN). Data on ferritin levels in these infants in the first 3 months of life are lacking. Objective of this study was to examine the course of iron status and incidence of iron deficiency and overload in neonates with alloimmune HDFN up to 3 months of age. Secondary objective was to analyse bilirubin levels, liver enzymes and red-blood-cell indices in the same time period and the association with intrauterine transfusion ( IUT). Materials and Methods Observational study of neonates with alloimmune HDFN admitted to our centre between November 2010 and March 2012. Data on iron status, bilirubin levels, liver enzymes and red-blood-cell indices up to 3 months of age were routinely collected and compared between neonates treated with and without IUT. Results Thirty-five infants with alloimmune HDFN were included. Iron overload occurred in 70% of neonates at birth and in 50% and 18% at the age of 1 and 3 months, respectively. No cases of iron deficiency at birth and only one case of iron deficiency at 3 months of age were found. No infants received iron therapy. Infants who received IUT had a significantly lower haemoglobin level and reticulocyte count and higher ferritin level at birth. Conclusion The vast majority of neonates with alloimmune HDFN have iron overload at birth. Incidence of iron overload gradually decreases within the first 3 months without iron supplementation. [ABSTRACT FROM AUTHOR]

Objective To evaluate the incidence and severity of and risk factors for thrombocytopenia at birth in neonates with red cell alloimmunization. Study design All neonates with haemolytic disease of the foetus/newborn (HDFN) due to red cell alloimmunization admitted to our centre between January 2000 and September 2010 were included in this retrospective study. We measured platelet counts at birth and determined the incidence of thrombocytopenia (platelet count < 150 × 109/l) and severe thrombocytopenia (platelet count < 50 × 109/l). Risk factors for thrombocytopenia at birth were evaluated. Results Thrombocytopenia was present in 26% (94/362) of included neonates with HDFN at birth. Severe thrombocytopenia was found in 6% (20/362) of neonates. Three risk factors were found to be independently associated with thrombocytopenia at birth: treatment with intrauterine red cell transfusion (IUT) (OR 3·32, 95% CI 1·67-6·60, P = 0·001), small for gestational age (SGA) below the 10th percentile (OR 3·32, 95% CI 1·25-8·80, P = 0·016) and lower gestational age at birth (OR 1·22/week, 95% CI 1·02-1·44, P = 0·025). Conclusions Thrombocytopenia at birth occurs in 26% of neonates with HDFN due to red cell alloimmunization and is independently associated with IUT treatment, SGA and lower gestational age at birth. [ABSTRACT FROM AUTHOR]

Monochorionic twins share a single placenta with intertwin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of several complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TTTS is characterized by the twin oligopolyhydramnios sequence, whereas TAPS is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in up to 5% of monochorionic twins and may also develop after incomplete laser treatment in TTTS cases. This review focuses on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS. In addition, we propose a classification system for antenatal and postnatal TAPS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the influence of fetoscopic laser therapy on fetal cardiac size in monochorionic twins complicated by twin-twin transfusion syndrome (TTTS). Methods: In a longitudinal, prospective study, we assessed fetal cardiac size sonographically in monochorionic diamniotic twins with TTTS treated by laser therapy and in monochorionic twins without TTTS. The fetal cardiothoracic ratio (cardiac circumference divided by thoracic circumference) of TTTS twins was determined within 24 h before, 12-24 h after and 1 week after laser treatment, and from then on every 2-4 weeks until birth. TTTS twins were classified into Quintero Stages 1-2 (n = 18) and Stages 3-4 (n = 16), and measurements were compared with biweekly measurements of non-TTTS monochorionic twins matched for gestational age (n = 38). Cardiomegaly was defined as a cardiothoracic ratio above the 97.5th percentile. Results: Before laser treatment, cardiomegaly was observed in 44% (8/18) and 50% (8/16) of recipients in Quintero Stages 1-2 and Stages 3-4, respectively. Cardiomegaly occurred in none of the donors before treatment. After laser treatment, cardiomegaly was observed in 76% (13/17) and 50% (7/14) of recipients in Stages 1-2 and Stages 3-4, respectively, and in 17% (3/18) and 13% (2/15) of donors in Stages 1-2 and Stages 3-4, respectively. Cardiomegaly was present in 18% (7/38) and 8% (2/25) of non-TTTS monochorionic twins and singletons. After laser therapy, the cardiothoracic ratio of recipients in Stages 1-2 and Stages 3-4 was not significantly changed (P = 0.34 and P = 0.67, respectively). The cardiothoracic ratio of donors in Stages 1-2 and Stages 3-4 was increased compared with that before laser therapy (P = 0.0002 and P = 0.005, respectively). Cardiothoracic ratios of non-TTTS monochorionic twins were not significantly different from our reference range in singletons throughout gestation, and were smaller than those in both recipients and donors after laser therapy. Conclusions: TTTS recipients show cardiomegaly before as well as after fetoscopic laser therapy for TTTS. Donors develop cardiomegaly only after laser treatment. Our findings emphasize the significant effect of TTTS and fetoscopic laser therapy on the fetal heart of both recipient and donor twins. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of fetal anemia and intrauterine transfusion on ventricular shortening fraction. Methods The end-diastolic and end-systolic transverse dimensions of the left and right ventricles were obtained using M-mode ultrasonography. The shortening fractions of both ventricles were calculated at three time points: before, immediately after and one day after intrauterine transfusion. The blood volume given at intrauterine transfusion was expressed as a percentage of estimated fetoplacental blood volume. Results Complete measurements were obtained from 49 transfusions in 23 fetuses. Intrauterine transfusion was performed at a median gestational age of 31 (range, 19–35) weeks. Median hemoglobin concentration before and after intrauterine transfusion was 7.9 (range, 2.7–13.7) g/dL and 14.3 (range, 12.7–16.1) g/dL, respectively. Both left and right ventricular shortening fractions differed significantly between the three time points. Left ventricular shortening fraction decreased immediately after transfusion in 43 (88%) of the 49 procedures. Right ventricular shortening fraction decreased immediately after transfusion in 42 (86%) of the 49 procedures. At the first intrauterine transfusion, there was only a weak correlation between the decrease in shortening fraction of both ventricles and the transfused volume (left: R2 = 0.15; P = 0.20/right: R2 = 0.005; P = 0.81). Conclusion Transfusion significantly decreases the shortening fraction of both ventricles of the fetal heart. There is, however, little correlation between the decrease in shortening fraction and the volume of red cells given at intrauterine transfusion. [ABSTRACT FROM AUTHOR]

Fetomaternal hemorrhage (FMH) can cause severe anemia in the fetus. Untreated, this may cause hydrops or even fetal death. However, correct diagnosis of FMH followed by blood transfusion can prevent these life-threatening consequences. We describe two cases in which fetal anemia was suspected because of maternal reporting of decreased or absent fetal movements, the detection of a sinusoidal heart rate pattern and increased blood flow velocities of the middle cerebral artery and umbilical vein. Together with the Betke-Kleihauer test showing fetal cells in the maternal circulation, this led to the correct diagnosis of severe fetal anemia caused by FMH. A Cesarean section was performed within a few hours. Both neonates were severely anemic and received immediate blood transfusions. They are currently alive and well. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic accuracy of amniotic fluid Delta OD 450 values in the second and third trimesters of D-alloimmunized pregnancies.Methods: We searched our database for singleton D-alloimmunized pregnancies with nonhydropic fetuses, where amniocentesis was performed within 4 days of first fetal blood sampling. Amniotic fluid Delta OD 450 values were plotted on an extrapolated Liley's chart. Sensitivity and specificity were calculated for two commonly used cutoff levels, Liley's zone 3 and the upper third of Liley's zone 2. Severe fetal anemia was defined as a hemoglobin concentration of more than 5 standard deviations below the normal mean for corresponding gestational age.Results: Seventy-nine pregnancies met our inclusion criteria. Overall accuracy of the extrapolated Liley's curve in predicting severe fetal anemia was 75% (95% confidence interval [CI] 64, 84) for zone 3 and 86% (95% CI 77, 93) when the upper third of zone 2 was included. Sensitivity of Delta OD 450 values in Liley's zone 3 or the upper third of Liley's zone 2 was 95% (95% CI 74, 100) before and 98% (95% CI 89, 100) after 27 weeks.Conclusion: Liley's extrapolated curve predicts severe fetal anemia with reasonable accuracy and high sensitivity. [ABSTRACT FROM AUTHOR]

ABSTRACT A 35-year-old primigravida, pregnant after in-vitro fertilization, was seen because of a trisomy 13/trisomy 18 ( T13/ T18) risk of 1:55, based on the result of her first-trimester combined test. She elected for non-invasive prenatal testing ( NIPT) at 14 + 5 weeks' gestation, which was positive for T13. After counseling, the patient elected to undergo amniocentesis. Quantitative fluorescence polymerase chain reaction ( QF-PCR) showed no signs of trisomy, and full karyotyping confirmed a normal 46,XY result. Analysis of the published literature on NIPT for T13 gives an overall detection rate of 91.6%, with a false-positive rate of 0.097%. Based on this detection rate, hypothetical calculations show that the positive predictive value is highly dependent on the prevalence of the disease, resulting in an unfavorable balance between benefit and harm in a general population. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of transabdominal amnioinfusion or no intervention on long-term outcomes in children born after second-trimester prelabour rupture of the membranes (PROM between 16+0/7 -24+0/7  weeks) and oligohydramnios.Population: Follow up of infants of women who participated in the randomised controlled trial: PPROMEXIL-III (NTR3492).Methods: Surviving infants were invited for neurodevelopmental assessment up to 5 years of corrected age using a Bayley Scales of Infant and Toddler Development or a Wechsler Preschool and Primary Scale of Intelligence. Parents were asked to complete several questionnaires.Main Outcome Measures: Neurodevelopmental outcomes were measured. Mild delay was defined as -1 standard deviation (SD), severe delay as -2 SD. Healthy long-term survival was defined as survival without neurodevelopmental delay or respiratory problems.Results: In the amnioinfusion group, 18/28 children (64%) died versus 21/28 (75%) in the no intervention group (relative risk 0.86; 95% confidence interval [CI] 0.60-1.22). Follow-up data were obtained from 14/17 (82%) children (10 amnioinfusion, 4 no intervention). In both groups, 2/28 (7.1%) had a mild neurodevelopmental delay. No severe delay was seen. Healthy long-term survival occurred in 5/28 children (17.9%) after amnioinfusion versus 2/28 (7.1%) after no intervention (odds ratio 2.50; 95% CI 0.53-11.83). When analysing data for all assessed survivors, 10/14 (71.4%) survived without mild neurodevelopmental delay and 7/14 (50%) were classified healthy long-term survivor.Conclusions: In this small sample of women suffering second-trimester PROM and oligohydramnios, amnioinfusion did not improve long-term outcomes. Overall, 71% of survivors had no neurodevelopmental delay.Tweetable Abstract: Healthy long-term survival was comparable for children born after second-trimester PROM and treatment with amnioinfusion or no intervention. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Velamentous cord insertion and vasa previa occur more frequently in monochorionic twin pregnancies than in singleton pregnancies. Both have been linked with poor perinatal outcome due to the increased risk of rupture of the velamentous vessels. We present a case of acute fetal distress in 2 fetuses in a monochorionic twin pregnancy caused by ruptured vasa previa that was not detected antenatally. Both infants were severely anemic at birth. Acute blood loss in twin 1 through the ruptured vessels, led to an acute feto-fetal transfusion from the co-twin through the placental vascular anastomoses. In monochorionic twins, ruptured vasa previa and acute hemorrhage in one fetus can lead to acute feto-fetal transfusion and result in severe hypovolemic shock and acute anemia in both fetuses. Increased awareness for vasa previa and the characteristic placental angioarchitecture in monochorionic twinning is of paramount importance. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Fetal megacystis presents a challenge in terms of counseling and management because of its varied etiology and evolution. The aim of this study was to present a comprehensive overview of the underlying etiologies and structural anomalies associated with fetal megacystis.Methods: This was a retrospective multicenter study of cases referred to the fetal medicine unit of one of the eight academic hospitals in The Netherlands with a diagnosis of fetal megacystis. For each case, data on and measurements of fetal urinary tract and associated structural anomalies were collected. All available postmortem examinations and postnatal investigations were reviewed in order to establish the final diagnosis. In the first trimester, fetal megacystis was defined as longitudinal bladder diameter (LBD) ≥ 7 mm, and in the second and third trimesters as an enlarged bladder failing to empty during an extended ultrasound examination lasting at least 40 min.Results: Of the 541 pregnancies with fetal megacystis, it was isolated (or solely accompanied by other signs of lower urinary tract obstruction (LUTO)) in 360 (67%) cases and associated with other abnormal ultrasound findings in 181 (33%) cases. The most common associated ultrasound anomaly was an increased nuchal translucency thickness (22%), followed by single umbilical artery (10%) and cardiac defect (10%). A final diagnosis was established in 418 cases, including 222 (53%) cases with isolated LUTO and 60 (14%) infants with normal micturition or minor isolated urological anomalies. In the remaining 136 (33%) cases, concomitant developmental or chromosomal abnormality or genetic syndrome was diagnosed. Overall, 40 chromosomal abnormalities were diagnosed, including trisomy 18 (n = 24), trisomy 21 (n = 5), Turner syndrome (n = 5), trisomy 13 (n = 3) and 22q11 deletion (n = 3). Thirty-two cases presented with anorectal malformations involving the anus, rectum and urogenital tract. In cases with confirmed urethral and anal atresia, megacystis occurred early in pregnancy and the bladder appeared severely distended (the LBD (in mm) was equal to or greater than twice the gestational age (in weeks)). Fetal macrosomia was detected in six cases and an overgrowth syndrome was detected in four cases, comprising two infants with Beckwith-Wiedemann syndrome and two with Sotos syndrome. Megacystis-microcolon-intestinal hypoperistalsis syndrome was diagnosed in five (1%) cases and prenatally suspected only in one case.Conclusions: Although the main cause of fetal megacystis is LUTO, an enlarged fetal bladder can also be present as a concomitant finding of miscellaneous genetic syndromes, developmental disturbances and chromosomal abnormalities. We provide an overview of the structural anomalies and congenital disorders associated with fetal megacystis and propose a practical guide for the differential diagnosis of genetic syndromes and chromosomal and developmental abnormalities in pregnancies presenting with fetal megacystis, focusing on the morphological examination of the fetus. © 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. [ABSTRACT FROM AUTHOR]

Objective: To propose a staging system for congenital lower urinary tract obstruction (LUTO) capable of predicting the severity of the condition and its prognosis.Methods: This was a national retrospective study carried out at the eight Academic Hospitals in The Netherlands. We collected prenatal and postnatal data of fetuses at high risk of isolated LUTO that were managed conservatively. Postnatal renal function was assessed by the estimated glomerular filtration rate (eGFR), calculated using the Schwartz formula, considering the length of the infant and the creatinine nadir in the first year after birth. Receiver-operating characteristics (ROC) curve analysis, univariate analysis and multivariate logistic regression analysis with stepwise backward elimination were performed in order to identify the best antenatal predictors of perinatal mortality and postnatal renal function.Results: In total, 261 fetuses suspected of having LUTO and managed conservatively were included in the study. The pregnancy was terminated in 110 cases and perinatal death occurred in 35 cases. Gestational age at appearance of oligohydramnios showed excellent accuracy in predicting the risk of perinatal mortality with an area under the ROC curve of 0.95 (P < 0.001) and an optimal cut-off at 26 weeks' gestation. Fetuses with normal amniotic fluid (AF) volume at 26 weeks' gestation presented with low risk of poor outcome and were therefore defined as cases with mild LUTO. In fetuses referred before the 26th week of gestation, the urinary bladder volume (BV) was the best unique predictor of perinatal mortality. ROC curve analysis identified a BV of 5.4 cm3 and appearance of oligohydramnios at 20 weeks as the best threshold for predicting an adverse outcome. LUTO cases with a BV ≥ 5.4 cm3 or abnormal AF volume before 20 weeks' gestation were defined as severe and those with BV < 5.4 cm3 and normal AF volume at the 20 weeks' scan were defined as moderate. Risk of perinatal mortality significantly increased according to the stage of severity, from mild to moderate to severe stage, from 9% to 26% to 55%, respectively. Similarly, risk of severely impaired renal function increased from 11% to 31% to 44%, for mild, moderate and severe LUTO, respectively.Conclusions: Gestational age at appearance of oligo- or anhydramnios and BV at diagnosis can accurately predict mortality and morbidity in fetuses with LUTO. Our proposed staging system can triage reliably fetuses with LUTO and predict the severity of the condition and its prognosis. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Twin pregnancy complicated by selective fetal growth restriction (sFGR) is associated with increased perinatal mortality and morbidity. Inconsistencies in the diagnostic criteria for sFGR employed in existing studies hinder the ability to compare or combine their findings. It is therefore challenging to establish robust evidence-based management or monitoring pathways for these pregnancies. The main aim of this study was to determine, by expert consensus using a Delphi procedure, the key diagnostic features of and the essential reporting parameters in sFGR.Methods: A Delphi process was conducted among an international panel of experts in sFGR in twin pregnancy. Panel members were provided with a list of literature-based parameters for diagnosing sFGR and were asked to rate their importance on a five-point Likert scale. Parameters were described as solitary (sufficient to diagnose sFGR, even if all other parameters are normal) or contributory (those that require other abnormal parameter(s) to be present for the diagnosis of sFGR). Consensus was sought to determine the cut-off values for accepted parameters, as well as parameters used in the monitoring, management and assessment of outcome of twin pregnancy complicated by sFGR. The questions were presented in two separate categories according to chorionicity.Results: A total of 72 experts were approached, of whom 60 agreed to participate and entered the first round; 48 (80%) completed all four rounds. For the definition of sFGR irrespective of chorionicity, one solitary parameter (estimated fetal weight (EFW) of one twin < 3rd centile) was agreed. For monochorionic twin pregnancy, at least two out of four contributory parameters (EFW of one twin < 10th centile, abdominal circumference of one twin < 10th centile, EFW discordance of ≥ 25%, and umbilical artery pulsatility index of the smaller twin > 95th centile) were agreed. For sFGR in dichorionic twin pregnancy, at least two out of three contributory parameters (EFW of one twin < 10th centile, EFW discordance of ≥ 25%, and umbilical artery pulsatility index of the smaller twin > 95th centile) were agreed.Conclusions: Consensus-based diagnostic features of sFGR in both monochorionic and dichorionic twin pregnancies, 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 © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To propose a clinical score for the optimal antenatal diagnosis of fetal lower urinary tract obstruction (LUTO) in the second and third trimesters of pregnancy, as an alternative to the commonly used ultrasound triad of megacystis, keyhole sign and hydronephrosis.Methods: This was a national retrospective study carried out at the eight tertiary fetal medicine units (FMUs) in The Netherlands. Only cases referred for megacystis from the second trimester onwards and with a clear postnatal diagnosis were included in the study. At referral, data were collected on amniotic fluid volume, renal cortical appearance, bladder volume, hydronephrosis, fetal ascites, ureteral size, keyhole sign, fetal sex and gestational age. Multivariate analysis was performed, starting by including all antenatal variables, and then excluding the weakest predictors using the backward stepwise strategy.Results: Over a 7-year period, 312 fetuses with a diagnosis of megacystis were referred to the eight Dutch tertiary FMUs. A final diagnosis was achieved in 143 cases, including 124 of LUTO and 19 reclassified after birth as non-obstructive megacystis. The optimal bladder volume cut-off for prediction of LUTO was 35 cm3 (area under the curve (AUC) = 0.7, P = 0.03). The clinical score formulated on the basis of the multivariate analysis included fetal sex, degree of bladder distension, ureteral size, oligo- or anhydramnios and gestational age at referral. The combination of these five variables demonstrated good accuracy in discriminating LUTO from non-obstructive megacystis (AUC = 0.84, P < 0.001), compared with the poor performance of the ultrasound triad (AUC = 0.63, P = 0.07).Conclusions: We propose a clinical score that combines five antenatal variables for the prospective diagnosis of congenital LUTO. This score showed good discriminative capacity in predicting LUTO, and better diagnostic accuracy compared with that of the classic ultrasound triad. Future studies to validate these results should be carried out in order to refine antenatal management of LUTO and prevent inappropriate fetal interventions. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Maternal alloimmunization to fetal red-blood-cell antigens is a major cause of fetal anemia, which can lead to hydrops and perinatal death if untreated. The cornerstone of management during pregnancy is intrauterine intravascular blood transfusion (IUT). Although this procedure is considered relatively safe, complications continue to occur. The aim of this study was to evaluate rates of procedure-related complications and perinatal loss following IUT, and their change over time, in order to identify factors leading to improved outcome.Methods: This was a retrospective analysis of all IUTs for red-cell alloimmunization performed at the national referral center for fetal therapy in The Netherlands, from 1988 to 2015. Differences in complication rates and their associations with alterations in transfusion technique after 2001 were assessed.Results: Between 1988 and 2015, 1678 IUTs were performed in 589 fetuses. For IUTs performed in 2001 and onwards, there was significant improvement in survival (88.6% vs 97.0%, P < 0.001) and a decline in procedure-related complications per fetus (9.8% vs 3.3%, P = 0.001) and per procedure (3.4% vs 1.2%, P = 0.003) compared with those performed before 2001. Procedure-related perinatal loss declined from 4.7% to 1.8% per fetus (P = 0.053). Beneficial changes in transfusion technique were routine use of fetal paralysis, increased use of intrahepatic transfusion and avoidance of arterial puncture.Conclusions: IUT has become an increasingly safe procedure in recent years when performed by experienced hands. The chosen technique should be fine-tuned according to the patient's individual situation. The declining complication rates are most likely related to center volume: this rare procedure is best performed in experienced fetal therapy centers. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

We conclude that currently available data do not indicate a major benefit of IUT for survival or brain injury risk in the anemic cotwin after SFD. Intrauterine transfusion (IUT) can correct successfully fetal anemia in the surviving cotwin after SFD; however, it is unclear if this treatment is beneficial for the long-term prognosis. Single fetal demise (SFD) in monochorionic (MC) twin pregnancy is associated with high risk of perinatal morbidity and mortality of the cotwin, including injury to the brain and other organs due to acute retrograde exsanguination1. [Extracted from the article]

Abstract: Objectives: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short‐term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2‐year infant outcome. Methods: The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety‐net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2‐year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety‐net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2‐year infant outcome. Results: One hundred and forty‐nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut‐off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut‐off) was 4% (interquartile range (IQR), 2–7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety‐net criteria) was 5% (IQR, 4–7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth‐weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short‐ or long‐term infant outcomes. Conclusion: The TRUFFLE study showed that a strategy of DV monitoring with safety‐net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2‐year infant survival without neurological impairment. This post‐hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety‐net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high‐risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV‐PI is within normal range. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome.Methods: The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety-net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2-year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety-net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2-year infant outcome.Results: One hundred and forty-nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut-off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2-7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety-net criteria) was 5% (IQR, 4-7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth-weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short- or long-term infant outcomes.Conclusion: The TRUFFLE study showed that a strategy of DV monitoring with safety-net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2-year infant survival without neurological impairment. This post-hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety-net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV-PI is within normal range. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Severe right ventricular outflow tract obstruction ( RVOTO) is a potential complication in recipient twins of twin-to-twin transfusion syndrome ( TTTS) that requires postnatal follow-up or treatment. We aimed to evaluate pregnancy characteristics of neonates with RVOTO from complicated monochorionic twin pregnancies, determine the incidence of RVOTO in TTTS cases and construct a prediction model for its development. Methods This was an observational cohort study of all complicated monochorionic twin pregnancies with a postnatal diagnosis of RVOTO examined at our center. Cases were referred for evaluation of the need for fetal therapy or intervention because of TTTS, selective intrauterine growth restriction ( sIUGR) or multiple congenital malformations in one of the twins. Ultrasound data were retrieved from our monochorionic twin database. Among liveborn TTTS recipients treated prenatally with laser therapy, those with RVOTO were compared with those without RVOTO (controls). We describe four additional cases with RVOTO that were not TTTS recipients. Results A total of 485 twin pregnancies received laser therapy for TTTS during the study period. RVOTO was diagnosed in 3% (11/368) of liveborn TTTS recipients, of whom two showed mild Ebstein's anomaly. Before laser therapy, pericardial effusion was seen in 45% (5/11) of RVOTO cases ( P < 0.01) and abnormal A-wave in the ductus venosus ( DV) in 73% (8/11) ( P = 0.03), significantly higher proportions than in controls. Mean gestational age at laser therapy was 17 + 3 weeks in RVOTO cases compared with 20 + 3 weeks in controls ( P = 0.03). A prediction model for RVOTO was constructed incorporating these three significant variables. One TTTS donor had RVOTO after the development of transient hydrops following laser therapy. Three larger twins in pregnancies complicated by sIUGR developed RVOTO, the onset of which was detectable early in the second trimester. Conclusions RVOTO occurs in TTTS recipient twins but can also develop in TTTS donors and larger twins of pregnancies complicated by sIUGR. Abnormal flow in the DV, pericardial effusion and early gestational age at onset of TTTS are predictors of RVOTO in TTTS recipients, which suggests increased vulnerability to hemodynamic imbalances in the fetal heart in early pregnancy. These findings could guide diagnostic follow-up protocols after TTTS treatment. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Vasa previa is a condition in which one or more fetal blood vessels run through the amniotic membranes and cross or run near the external orifice of the uterus. Rupture of membranes can lead to tearing of these vessels and cause acute fetal exsanguination. In monochorionic twin (MC) pregnancies, acute exsanguination in one twin can lead to severe complications in the co-twin due to the presence of inter-twin placental vascular connections. We report a MC pair with severe perinatal asphyxia due to acute exsanguination after prenatally undetected ruptured vasa previa. This resulted in severe hemorrhagic shock in both twins with double fatal outcome. Antenatal detection of vasa previa is of paramount importance to prevent severe morbidity and mortality, especially in MCs. A review of the literature is presented. [ABSTRACT FROM AUTHOR]