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Objective: To evaluate the neurodevelopmental outcome at school age in children newly diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT). Study design: This observational cohort study included children diagnosed with FNAIT between 2002 and 2014. Children were invited for cognitive and neurological testing. Behavioral questionnaires and school performance results were obtained. A composite outcome of neurodevelopmental impairment (NDI) was used, defined, and subdivided into mild-to-moderate and severe NDI. Primary outcome was severe NDI, defined as IQ

Objective: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from maternal platelet-directed antibodies which can cause severe intracranial haemorrhage (ICH) in fetuses and new-borns. Screening for human platelet antigen-1a (HPA-1a) directed antibodies during pregnancy could allow for timely intervention with antenatal treatment and prevent the occurrence of ICH. We aim to assess the cost-effectiveness of adding screening for anti-HPA-1a to the prenatal screening program. Design: A decision analysis model was developed. Setting: The Netherlands. Population: 171,713 pregnant women. Methods: Lifetime costs and effects of antenatal anti-HPA-1a screening with subsequent diagnostic and treatment interventions were compared to the current situation without screening in the Netherlands. Model parameters were based on literature and expert opinions. One-way-sensitivity analysis and probabilistic sensitivity analysis were performed. Main Outcome Measures: Incremental cost-effectiveness ratio (ICER). Results: Adding screening for HPA-1a antibodies to the current antenatal screening program of the Netherlands will lead to an additional cost of 4.7 million euro and a gain of 226 Quality-Adjusted Life Years (QALY) per year, indicating an ICER of \euro20,782 per QALY gained. One-way sensitivity analysis showed that the uncertainty around the incidence of ICH, lifetime costs of disabled children and the probability of having antibody quantitation >3.0 IU/ml at 20 weeks had the highest effect on the ICER. Conclusion: Antenatal HPA-1a screening might be cost-effective. To obtain more knowledge and thereby reduce the uncertainty on risk stratification, a pilot screening program is warranted. Funding: Sanquin

Contains fulltext : 244602.pdf (Publisher’s version ) (Open Access) AIM OF THE STUDY: Outcome of fetuses, prenatally diagnosed with sacrococcygeal teratoma (SCT), is still poorly documented. This study assesses the incidence and prenatal predictors of outcome in all fetuses prenatally diagnosed with SCT. METHODS: This is a retrospective study on all fetuses prenatally diagnosed with SCT from 1998 to 2018 in the Netherlands. Poor outcome was defined as terminations of pregnancy (TOP) because of expected unfavorable outcome, intrauterine fetal death, or early neonatal death. Potential risk factors for poor outcome were analyzed. MAIN RESULTS: Eighty-four fetuses were included. Sixteen (19.0%) TOPs were excluded from statistical analysis. Eleven of the remaining 68 fetuses had poor outcome. Overall mortality was 32.1%, with a mortality excluding TOPs of 13.1%. Thirteen fetal interventions were performed in 11 (13.1%) fetuses. Potential risk factors for poor outcome were the presence of fetal hydrops (OR: 21.0, CI: 2.6-275.1, p = 0.012) and cardiomegaly (OR: 10.3, CI: 1.9-55.8, p = 0.011). CONCLUSIONS: The overall mortality of fetuses prenatally diagnosed with SCTs including tTOP was 32.1%. This high mortality rate was mainly due to termination of pregnancy. Mortality excluding TOP was 13.1%. Potential risk factors for poor outcome were fetal hydrops and cardiomegaly.

Background Children affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT) are at risk of severe intracranial haemorrhage. Management in the postnatal period is based on sparse evidence. We aimed to describe the contemporary management and outcomes of patients with FNAIT in high-income countries.Methods In this multicentre, retrospective, cohort study, we set up a web-based registry for the collection of deidentified data on the management and course of neonates with FNAIT. Eight centres from seven countries (Australia, Norway, Slovenia, Spain, Sweden, the Netherlands, and the USA) participated. Eligibility criteria comprised neonates with FNAIT being liveborn between Jan 1, 2010, and Jan 1, 2020; anti-human platelet antigen (HPA) alloantibodies in maternal serum; confirmed maternal and fetal HPA incompatibility; and bleeding detected at antenatal ultrasound, neonatal thrombocytopenia (

Introduction Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in the fetus and newborn. Adequate screening programs allow for timely prevention and intervention resulting in significant reduction of the disease over the last decades. Nevertheless, HDFN still occurs and with current treatment having reached an optimum, focus shifts toward noninvasive therapy options. Areas covered This review focusses on the timely identification of high risk cases and antenatal management. Furthermore, we elaborate on future perspectives including improvement of screening, identification of high risk cases and promising treatment options. Expert opinion In high-income countries mortality and morbidity rates due to HDFN have drastically been reduced over the last decades, yet worldwide anti-D mediated HDFN still accounts for 160,000 perinatal deaths and 100,000 patients with disabilities every year. Much of these deaths and disabilities could have been avoided with proper identification and prophylaxis. By implementing sustainable prevention, screening, and disease treatment measures in all countries this will systemically reduce unnecessary perinatal deaths. There is a common responsibility to engage in this cause.

BACKGROUND: Children with fetal and neonatal alloimmune throm-bocytopenia face increased risk of intracranial hemorrhage potentially leading to developmental impairment. To prevent intracranial hemorrhage, pregnant women with alloantibodies against fetal platelets are often treated with intravenous immunoglobulin. Intravenous immunoglobulin seems effective in vastly reducing the risk of fetal or neonatal bleeding complications. However, information on long-term neurodevelopment of these children is lacking. OBJECTIVE: This study aimed to evaluate long-term neurodevelopmental outcome in children with fetal and neonatal alloimmune thrombocytopenia who were treated with intravenous immunoglobulin antenatally. STUDY DESIGN: An observational cohort study was performed, including children of mothers treated with intravenous immunoglobulin during pregnancy because a previous child was diagnosed with fetal and neonatal alloimmune thrombocytopenia. Children were invited for a follow-up assessment including standardized cognitive and neurologic tests. The parents were asked to complete a behavioral questionnaire and school performance reports. The primary outcome was severe neurodevelopmental impairment, defined as severe cognitive impairment (intelligence quotient = 3, bilateral blindness, and/or bilateral deafness (requiring amplification). The secondary outcome was mild to moderate neurodevelopmental impairment, defined as either mild to moderate cognitive impairment (intelligence quotient

Objective: Low fetal fraction (LFF) in prenatal cell-free DNA (cfDNA) testing is an important cause of test failure and no-call results. LFF might reflect early abnormal placentation and therefore be associated with adverse pregnancy outcome. Here, we review the available literature on the relationship between LFF in cfDNA testing and adverse pregnancy outcome. Method: A systematic literature search was conducted in MEDLINE and EMBASE up to November 1, 2020. Results: Five studies met the criteria for inclusion; all were retrospective observational cohort studies. The cohort sizes ranged from 370 to 6375 pregnancies, with all tests performed in the first trimester or early second trimester. A 4% cutoff for LFF was used in two studies, two studies used the 5th and 25th percentiles, respectively, and one study used a variety of cutoff values for LFF. LFF in prenatal cfDNA testing was observed to be associated with hypertensive disease of pregnancy, small for gestational age neonates, and preterm birth. Conflicting results were found regarding the association between LFF and gestational diabetes mellitus. Conclusions: LFF in cfDNA testing is associated with adverse pregnancy outcome,specifically pregnancy-related hypertensive disorders, preterm birth, and impaired fetal growth related to placental dysfunction. Since the available evidence is limited, a large prospective cohort study on the relationship between fetal fraction and pregnancy outcomes is needed.

Since the completion of the Management of Myelomeningocoele Study, maternal‐fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high‐grade evidence., Key Points What's already known about this topic? The use of fetoscopy for spina bifida repair is adopted by an increasing number of centers worldwide. On the other hand, its efficacy has not been established within a randomized controlled trial and thus it is still considered experimental by others. What does this study add? Herein we describe a framework which could be used to determine the developmental stage of novel interventions in the field of maternal‐fetal surgery. Furthermore, we discuss the difficulties of gathering high level evidence for a fetoscopic closure of the spinal defect in fetuses with a spina bifida.

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.

Objective To compare the prevalence of intermittent absent or reversed end‐diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome. Methods The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated. Results iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)‐anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co‐twin, another underwent early premature emergency section for fetal distress. Conclusion iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.

Background and Objectives Alloantibodies against red-blood-cell (RBC) antigens often coincide with alloantibodies against leucocytes and platelets and sometimes with autoantibodies towards various antigens. Chimerism may be one of the factors responsible for the combination of allo- and autoantibodies. Women with alloantibodies against RBC antigens causing haemolytic disease of the fetus and neonate may need to receive intrauterine transfusions. These transfusions increase not only maternal antibody formation but also fetomaternal bleeding and may enhance fetal chimerism. We determined the prevalence of and risk factors for autoantibodies against some common clinical target antigens, in alloimmunized women after IUT.Materials and Methods We tested for autoantibodies against RBC, anti-thyroid peroxidase, anti-extractable nuclear antigens, anti-cyclic citrullinated proteins and anti-tissue transglutaminase. Women with and without autoantibodies were compared for age; number of RBC alloantibodies, pregnancies and IUTs, and other factors that may play a role in immunization.Results Non-RBC-targeted autoantibodies were present in 40 of 258 tested women (15 center dot 5%, with 90% anti-TPO specificity), comparable to the prevalence reported in healthy Dutch women of these ages. Surprisingly, compared with women who had a single RBC alloantibody, a significantly higher proportion of women with multiple RBC alloantibodies had autoantibodies (5 center dot 3% and 18 center dot 4%, respectively; odds ratio 4 center dot 06, 95% CI: 1 center dot 20-13 center dot 7). Other characteristics of women with and without autoantibodies were not different.Conclusion Multiple RBC alloantibodies after extensive allogeneic exposure during pregnancy and presumed increased fetomaternal chimerism are not associated with (selected) autoantibodies. Lack of allo-RBC multi-responsiveness seems associated with decreased auto(-TPO) antibody formation.

Objective To investigate whether perioperative fetal hemodynamic changes in twin‐to‐twin transfusion syndrome (TTTS) are associated with neurodevelopmental impairment (NDI) at two years. Methods Doppler parameters of three sonograms (day before, first day after and 1 week after laser surgery for TTTS) were assessed for correlation with neurodevelopmental outcome at two years (2008‐2016). NDI was defined as: cerebral palsy, deafness, blindness, and/or a Bayley‐III cognitive/motor developmental test‐score > 2SD below the mean. Results Long‐term outcome was assessed in 492 TTTS survivors. NDI was present in 5% (24/492). After adjustment for severe cerebral injury (present in 4%), associated with NDI were: middle cerebral artery peak systolic velocity (MCA‐PSV) >1.5 multiples of the median (MoM) 1 day after surgery (odds ratio [OR] 4.96; 95% confidence interval [CI]: 1.17‐21.05, P = .03), a change from normal umbilical artery pulsatility index (UA‐PI) presurgery to UA‐PI >p95 postsurgery (OR 4.19; 95% CI: 1.04‐16.87, P = .04), a change from normal to MCA‐PSV >1.5MoM (OR 4.75; 95% CI: 1.43‐15.77, P = .01). Conclusion Perioperative fetal hemodynamic changes in TTTS pregnancies treated with laser are associated with poor neurodevelopmental outcome. Prospective research on the cerebrovascular response to altered hemodynamic conditions is necessary to further understand the cerebral autoregulatory capacity of the fetus in relation to neurodevelopmental outcome.

Introduction: Invasive fetal cardiac intervention (FCI) for pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (PS) has been performed with small single-institution series reporting technical and physiological success. We present the first multicenter experience. Objectives: Describe fetal and maternal characteristics of those being evaluated for FCI, including pregnancy/neonatal outcome data using the International Fetal Cardiac Intervention Registry (IFCIR). Methods: We queried the IFCIR for PAIVS/PS cases evaluated from January 2001 to April 2018 and reviewed maternal/fetal characteristics, procedural details, pregnancy and neonatal outcomes. Data were analyzed using standard descriptive statistics. Results: Of the 84 maternal/fetal dyads in the registry, 58 underwent pulmonary valvuloplasty at a median gestational age of 26.1 (21.9–31.0) weeks. Characteristics of fetuses undergoing FCI varied in terms of tricuspid valve (TV) size, TV regurgitation, and pulmonary valve patency. There were fetal complications in 55% of cases, including 7 deaths and 2 delayed fetal losses. Among those who underwent successful FCI, the absolute measurement of the TV increased by 0.32 (±0.17) mm/week from intervention to birth. Among 60 liveborn with known outcome, there was a higher percentage having a biventricular circulation following successful FCI (87 vs. 43%). Conclusions: Our data suggest a possible benefit to fetal therapy for PAIVS/PS, though rates of technically unsuccessful procedures and procedure-related complications, including fetal loss were substantial. FCI criteria are extremely variable, making direct comparison to nonintervention patients challenging and potentially biased. More uniform FCI criteria for fetuses with PAIVS/PS are needed to avoid unnecessary procedures, expose only fetuses most likely to sustain a benefit, and to enable comparisons to be made with nonintervention patients.

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

Fetal neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloantibodies directed against the human platelet antigens (mostly HPA-1a or HPA-5b) of the (unborn) child and can lead to severe bleeding. Anti-HPA-1a-mediated FNAIT shows a severe clinical outcome more often than anti-HPA-5b-mediated FNAIT. Given the relatively high prevalence of anti-HPA-5b in pregnant women, the detection of anti-HPA-5b in FNAIT-suspected cases may in some cases be an incidental finding. Therefore we investigated the frequency of anti-HPA-5b-associated severe bleeding in FNAIT. We performed a retrospective nationwide cohort study in cases with clinical suspicion of FNAIT. HPA antibody screening was performed using monoclonal antibody-specific immobilisation of platelet antigens. Parents and neonates were typed for the cognate antigen. Clinical data were collected by a structured questionnaire. In 1 864 suspected FNAIT cases, 161 cases (8 center dot 6%) had anti-HPA-1a and 60 (3 center dot 2%) had anti-HPA-5b. The proportion of cases with severe bleeding did not differ between the cases with anti-HPA-1a (14/129; 11%) and anti-HPA-5b (4/40; 10%). In multigravida pregnant women with a FNAIT-suspected child, 100% (81/81) of anti-HPA-1a cases and 79% (38/48) of anti-HPA-5b cases were HPA-incompatible, whereas 86% and 52% respectively were expected, based on the HPA allele distribution. We conclude that anti-HPA-5b can be associated with severe neonatal bleeding symptoms. A prospective study is needed for true assessment of the natural history of anti-HPA-5b mediated FNAIT.

Objective: To evaluate which risk factors for RhD immunization remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. Assessment of the prevalence of RhD immunizations. Design: Prospective cohort Setting: The Netherlands. Population: Two-year nationwide cohort. Methods: RhD-negative women in their first RhD immunized pregnancy and their foregoing non-immunized pregnancy. Risk factors for RhD immunization were compared with population data. Main outcomes measures: Risk factors for FMH and subsequently RhD immunization, prevalence of RhD immunizations. Results: The prevalence of newly detected RhD immunizations was 0.31% (79/25,170) of all RhD-negative pregnant women in the Netherlands. After exclusion, 193 women remained. Significant risk factors found in the group of 113 parous women (previous pregnancy >16 weeks, RhD positive child) 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 over 42 weeks (OR 6.1, 95% CI 2.2-16.6), postnatal bleeding (>1000mL) (OR 2.0 95% CI 1.1-3.6), surgical removal of the placenta (SRP) (OR 4.3, 95% CI 2.0-9.3). The miscarriage rate in the group of women without a previous RhD positive child was significantly higher than in the Dutch population (35% vs 12.5% p

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.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.

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 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 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 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 0.5 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.

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 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 (c) 2018 ISUOG. Published by John Wiley & Sons Ltd.

Objectives To explore whether intertwin discordance in myocardial performance index (MPI) or cardiac time intervals enables the prediction of twin-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) pregnancies with amniotic fluid discordance. Methods Prospective cohort study of MCDA pregnancies with amniotic fluid discordance ≥4 cm. Serial ultrasound examinations consisted of evaluation of amniotic fluid, fetal Dopplers and fetal cardiac function. Results We included 21 "future-TTTS" (group I), 18 selective fetal growth restriction (sFGR; group II) and 20 uncomplicated MCDA twin pairs (group III). Group I had a higher intertwin difference in left ventricle (LV) MPI and right ventricle (RV) MPI compared to group II and III. The intertwin difference in global heart relaxation time was significantly higher in group I compared to group III. Future recipient twins had significantly higher relaxation times of the global heart and RV and lower contraction times of the global heart and RV compared to the "expected recipients" in group II and III. Conclusion Intertwin discordance in LV-MPI and RV-MPI differentiate between TTTS and MCDA pregnancies with transient discordant amniotic fluid volume. Cardiac time intervals identify future recipient twins. The clinical utility of cardiac time intervals and MPI should be investigated in large prospective studies.

Twin anemia polycythemia sequence (TAPS) is a form of chronic imbalanced feto-fetal transfusion through minuscule placental anastomoses leading to anemia in the TAPS donor and polycythemia in the TAPS recipient and has been reported only in monochorionic twins. We report a very unusual case of TAPS which developed in a dichorionic twin pair, born at a gestational age of 33+2. Twin 1 (recipient) was polycythemic and had a hemoglobin value of 22.4 g/dL, whereas twin 2 (donor) was anemic with a hemoglobin value of 9.8 g/dL and an increased reticulocyte count (72‰). Color dye injection of the placenta revealed the presence of a deep-hidden small veno-venous anastomosis. Dichorionicity was confirmed on histologic examination. Aside from respiratory distress syndrome, the donor twin had an uncomplicated neonatal course. The recipient twin developed a post-hemorrhagic ventricular dilatation requiring treatment with a ventriculoperitoneal shunt and Rickham reservoir. This report shows that in dichorionic twins, placental anastomoses can be present, which can lead to the development of TAPS with severe consequences. Therefore, when a pale and plethoric dichorionic twin pair is born, a complete diagnostic work-up is required, including a full blood count with reticulocytes and placental injection, to investigate the presence and nature of potential underlying feto-fetal transfusion. Once the diagnosis of TAPS has been established, cerebral ultrasound, hearing screening, and long-term follow-up are strongly recommended as these twins have increased risk for severe cerebral injury, hearing loss, and long-term neurodevelopmental impairment.

Background and objectives Guidelines and indications for exchange transfusion in haemolytic disease of the foetus and newborn (HDFN) have changed drastically in the past decades, causing a decline in exchange transfusion rate. This study aims to evaluate the incidence of exchange transfusions (ETs) in neonates with Rh-mediated HDFN over the past 20 years at our centre, and report potentially ET-related complications as well as indicators for bilirubin encephalopathy.Material and methods In this observational study, 438 neonates were included with HDFN, born >= 35 weeks gestational age at the Leiden University Medical Centre between January 2000 and July 2020. The incidence of ET and procedure-related complications were assessed in three consecutive time periods determined by changes in guidelines and indications for ET.Results The incidence of ET in our centre declined from (104/156) 67% (time period 2000-2005), to (39/181) 22% (2006-2015) and to (10/101) 10% (2015-2020, p < 0 center dot 001). The maximum bilirubin levels in neonates after birth increased from 13 center dot 6 mg/dL (or 233 mu mol/L), to 15 center dot 0 mg/dL (257 mu mol/L) and to 15 center dot 3 mg/dL (263 mu mol/L). The incidence of complications associated with the use of ET (including sepsis, haematologic disorders and respiratory failure) remained stable throughout the years, and no neonates died during the study period.Conclusion Exchange transfusion incidence declined significantly over the past two decades. Decrease in ET incidence, and concomitant decrease in exposure and expertise, was not associated with an increase in procedure-related complications.

Background: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. Objective: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. Study Design: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. Results: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7–28.8; range, 15.1–35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P, SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND Fetal bilirubin is routinely measured at our center when taking a pretransfusion blood sample at intrauterine transfusions in hemolytic disease of the fetus and newborn. However, the clinical value of fetal bilirubin assessment is not well known, and the information is rarely used. We speculated that there could be a role for this measurement in predicting the need for neonatal exchange transfusion. OBJECTIVE This study aimed to evaluate the predictive value of fetal bilirubin for exchange transfusions in severe hemolytic disease of the fetus and newborn. STUDY DESIGN A total of 186 infants with Rh alloantibody–mediated hemolytic disease of the fetus and newborn treated with one or more intrauterine transfusions at the Leiden University Medical Center between January 2006 and June 2020 were included in this observational study. Antenatal and postnatal factors were compared between infants with and without exchange transfusion treatments. The primary outcome was the fetal bilirubin levels before the last intrauterine transfusion in relation to the need for exchange transfusion. RESULTS In a multivariate logistic regression analysis, the fetal bilirubin level before the last intrauterine transfusions (odds ratio, 1.32; 95% confidence interval, 1.09–1.61 per 1 mg/dL) and the total number of intrauterine transfusions (odds ratio, 0.63; 95% confidence interval, 0.44–0.91 per intrauterine transfusion) were independently associated with the need for exchange transfusion. The area under the curve was determined at 0.71. A Youden index was calculated at 0.43. The corresponding fetal bilirubin level was 5 mg/dL and had a sensitivity of 79% and a specificity of 64%. CONCLUSION A high fetal bilirubin level before the last intrauterine transfusion was associated with a high likelihood of neonatal exchange transfusion.

Background Selective fetal restriction growth (sFGR) is one of the common diseases of monochorionic diamniotic (MCDA) twin pregnancies, resulting in many adverse outcomes. At present, second trimester ultrasonography is widely used in the prenatal diagnosis of sFGR, but the diagnostic effectiveness is still uncertain. The aim of this study is to assess the diagnostic accuracy of second trimester Doppler ultrasound measurements for sFGR. Methods A retrospective study included 280 pregnant women (118 with and 162 without sFGR) with MCDA pregnancies was conducted in the fetal medicine center from Leiden University Medical Center from January 2008 to December 2013. The women participating had already undergone an ultrasound examination in the second trimester. The postnatal criteria of sFGR was a single birth weight (BW) 95th percentile). According to the diagnosis of sFGR after birth, we evaluate diagnostic effectiveness of Doppler ultrasound in the second trimester for sFGR. Results Of these 280 participants, the mean age was 32.06 ± 4.76 years. About 43.9% of pregnant women were primiparas. The ability of second trimester Doppler ultrasound to accurately diagnosed sFGR is 75.4%, missed diagnosis rate and the misdiagnosis rate were 24.6% and 10.5% respectively. The ROC curve indicated that the combination of AC discordance, EFW discordance, and small fetal UA blood flow was the best diagnostic indicator of sFGR in MCDA pregnancy with the AUC was 0.882 (95%CI, 0.839–0.926). Conclusions Second trimester Doppler and ultrasound measurements is an effective method for early prenatal diagnosis of sFGR. The combined indicator of AC discordance, EFW discordance, and the small fetal UA blood flow reaches highest diagnostic value.

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., Tweetable abstract Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention.