ObjectiveTo investigate the association between epidural analgesia (EDA) vs patient-controlled remifentanil analgesia (PCRA) and emergency delivery for presumed fetal compromise, in relation to... Show moreObjectiveTo investigate the association between epidural analgesia (EDA) vs patient-controlled remifentanil analgesia (PCRA) and emergency delivery for presumed fetal compromise, in relation to birth-weight quintile.MethodsThis was a post-hoc per-protocol analysis of the RAVEL multicenter equivalence randomized controlled trial. Non-anomalous singleton pregnancies between 36 + 0 and 42 + 6 weeks' gestation were randomized at the time of requesting pain relief to receive EDA or PCRA. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included mode of delivery and neonatal outcomes. Analysis was performed according to birth-weight quintile and was corrected for relevant confounding variables.ResultsOf 619 pregnant women, 336 received PCRA and 283 received EDA. Among women receiving EDA, 14.8% had an emergency delivery for presumed fetal compromise, compared with 8.3% of women who received PCRA. After adjusting for parity, women receiving EDA had higher odds of presumed fetal compromise compared to those receiving PCRA (odds ratio, 1.69 (95% CI, 1.01-2.83)). A statistically significant linear-by-linear association was observed between presumed fetal compromise and birth-weight quintile (P = 0.003). The incidence of emergency delivery for presumed fetal compromise was highest in women receiving EDA and delivering a neonate with a birth weight in the lowest quintile.ConclusionsIntrapartum EDA is associated with a higher rate of emergency delivery for presumed fetal compromise compared to treatment with PCRA. Birth-weight quintile is a strong predictor of this outcome, independent of pain management method. (c) 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Show less
Objective Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late... Show moreObjective Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies.Methods This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention.Results Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124).Conclusion Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. (c) 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Show less
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... Show moreThe 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. (c) 2022 International Society of Ultrasound in Obstetrics and Gynecology. Show less
Objectives: Fetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question,... Show moreObjectives: Fetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question, FGR singletons have been compared primarily to matched appropriately grown singletons, a design which is inherently biased by differences in genetic and maternal factors. To overcome these limitations, we conducted a within-pair comparison of neonatal structural cerebral ultrasound measurements in monochorionic twin pairs with selective FGR (sFGR). Methods: Structural cerebral measurements on neonatal cerebral ultrasound were compared between the smaller and larger twins of monochorionic twin pairs with sFGR, defined as a birth-weight discordance (BWD) >= 20%, born in our center between 2010 and 2020. Measurements from each twin pair were also compared with those of an appropriately grown singleton, matched according to sex and gestational age at birth. Results: Included were 58 twin pairs with sFGR, with a median gestational age at birth of 31.7 (interquartile range, 29.9-33.8) weeks and a median birth weight of 1155 g for the smaller twin and 1725 g for the larger twin (median BWD, 32%). Compared with both the larger twin and the singleton, the smaller twin had significantly smaller cerebral structures (corpus callosum, vermis, cerebellum), less white/deep gray matter and smaller intracranial surface area and volume. Intracranial-volume discordance and BWD correlated significantly (R-2 = 0.228, P < 0.0001). The median intracranial-volume discordance was smaller than the median BWD (19% vs 32%, P < 0.0001). After correction for intracranial volume, only one of the observed differences (biparietal diameter) remained significant for the smaller twin vs both the larger twin and the singleton. Conclusions: In monochorionic twins with sFGR, neonatal cerebral ultrasound reveals an overall, proportional restriction in brain growth, with smaller cerebral structures, less white/deep gray matter and smaller overall brain-size parameters in the smaller twin. There was a positive linear relationship between BWD and intracranial-volume discordance, with intracranial-volume discordance being smaller than BWD. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology. Show less
Objective Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify... Show moreObjective Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify predictors of fetal death in these pregnancies. Methods This was an international multicenter retrospective cohort study. Type-III sFGR was defined as fetal estimated fetal weight (EFW) of one twin below the 10(th) percentile and intertwin EFW discordance of >= 25% in combination with intermittent absent or reversed end-diastolic flow in the umbilical artery of the smaller fetus. Predictors of fetal death were recorded longitudinally throughout gestation and assessed in univariable and multivariable logistic regression models. The classification and regression trees (CART) method was used to construct a prediction model of fetal death using significant predictors derived from the univariable analysis. Results A total of 308 twin pregnancies (616 fetuses) were included in the analysis. In 273 (88.6%) pregnancies, both twins were liveborn, whereas 35 pregnancies had single (n = 19 (6.2%)) or double (n = 16 (5.2%)) fetal death. On univariable analysis, earlier gestational age at diagnosis of Type-III sFGR, oligohydramnios in the smaller twin and deterioration in umbilical artery Doppler flow were associated with an increased risk of fetal death, as was larger fetal EFW discordance, particularly between 24 and 32 weeks' gestation. None of the parameters identified on univariable analysis maintained statistical significance on multivariable analysis. The CART model allowed us to identify three risk groups: a low-risk group (6.8% risk of fetal death), in which umbilical artery Doppler did not deteriorate; an intermediate-risk group (16.3% risk of fetal death), in which umbilical artery Doppler deteriorated but the diagnosis of sFGR was made at or after 16 + 5 weeks' gestation; and a high-risk group (58.3% risk of fetal death), in which umbilical artery Doppler deteriorated and gestational age at diagnosis was < 16 + 5 weeks' gestation. Conclusions Type-III sFGR is associated with a high risk of fetal death. A prediction algorithm can help to identify the highest-risk group, which is characterized by Doppler deterioration and early referral. Further studies should investigate the potential benefit of fetal surveillance and intervention in this cohort. (c) 2022 International Society of Ultrasound in Obstetrics and Gynecology. Show less
Shinar, S.; Xing, W.; Lewi, L.; Slaghekke, F.; Yinon, Y.; Raio, L.; ... ; Mieghem, T. van 2022
Objectives: Little is known regarding fetal growth patterns in monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction (sFGR). We aimed to assess fetal growth and... Show moreObjectives: Little is known regarding fetal growth patterns in monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction (sFGR). We aimed to assess fetal growth and umbilical artery Doppler pattern in Type-III sFGR across gestation and evaluate the effect of changing Doppler flow pattern on growth and intertwin growth discordance. Methods: This was a retrospective cohort study of all Type-III sFGR pregnancies managed at nine fetal centers over a 12-year time period. Higher-order multiple pregnancy and cases with major fetal anomaly or other monochorionicity-related complications at presentation were excluded. Estimated fetal weight (EFW) was assessed on ultrasound for each twin pair at five timepoints (16- 20, 21- 24, 25- 28, 29- 32 and > 32 weeks' gestation) and compared with singleton and uncomplicated monochorionic twin EFW. EFW and intertwin EFW discordance were compared between pregnancies with normalization of umbilical artery Doppler of the smaller twin later in pregnancy and those with persistently abnormal Doppler. Results: Overall, 328 pregnancies (656 fetuses) met the study criteria. In Type-III sFGR, the smaller twin had a lower EFW than an average singleton fetus (EFW Z-score ranging from -1.52 at 16 weeks to -2.69 at 36 weeks) and an average monochorionic twin in uncomplicated pregnancy (Z-score ranging from -1.73 at 16 weeks to -1.49 at 36 weeks) throughout the entire gestation, while the larger twin had a higher EFW than an average singleton fetus until 22 weeks' gestation and was similar in EFW to an average uncomplicated monochorionic twin throughout gestation. As pregnancy advanced, growth velocity of both twins decreased, with the larger twin remaining appropriately grown and the smaller twin becoming more growth restricted. Intertwin EFW discordance remained stable throughout gestation. On multivariable longitudinal modeling, normalization of fetal umbilical artery Doppler was associated with better growth of the smaller twin (P= 0.002) but not the larger twin ( P= 0.1), without affecting the intertwin growth discordance (P= 0.09). Conclusions: Abnormal fetal growth of the smaller twin in Type-III sFGR was evident early in pregnancy, while EFW of the larger twin remained normal throughout gestation. Normalization of umbilical artery Doppler was associated with improved fetal growth of the smaller twin. (C) 2021 International Society of Ultrasound in Obstetrics and Gynecology. Show less
Rennert, K.N.; Breuking, S.H.; Schuit, E.; Bekker, M.N.; Woiski, M.; Boer, M.A. de; ... ; Hermans, F.J.R. 2021
Objective To assess the association between preterm birth and cervical length after arrested preterm labor in high-risk pregnant women.Methods In this post-hoc analysis of a randomized clinical... Show moreObjective To assess the association between preterm birth and cervical length after arrested preterm labor in high-risk pregnant women.Methods In this post-hoc analysis of a randomized clinical trial, transvaginal cervical length was measured in women whose contractions had ceased 48 h after admission for threatened preterm labor. At admission, women were defined as having a high risk of preterm birth based on a cervical length of < 15 mm or a cervical length of 15-30 mm with a positive fetal fibronectin test. Logistic regression analysis was used to investigate the association of cervical length measured at least 48 h after admission and of the change in cervical length between admission and at least 48 h later, with preterm birth before 34 weeks' gestation and delivery within 7 days after admission.Results A total of 164 women were included in the analysis. Women whose cervical length increased between admission for threatened preterm labor and 48 h later (32%; n=53) were found to have a lower risk of preterm birth before 34weeks compared with women whose cervical length did not change (adjusted odds ratio (aOR), 0.24 (95% CI, 0.09-0.69)). The risk in women with a decrease in cervical length between the two time points was not different from that in women with no change in cervical length (aOR, 1.45 (95% CI, 0.62-3.41)). Moreover, greater absolute cervical length after 48 h was associated with a lower risk of preterm birth before 34 weeks (aOR, 0.90 (95% CI, 0.84-0.96)) and delivery within 7 days after admission (aOR, 0.91 (95% CI, 0.82-1.02)). Sensitivity analysis in women randomized to receive no intervention showed comparable results.Conclusion Our study suggests that the risk of preterm birth before 34weeks is lower in women whose cervical length increases between admission for threatened preterm labor and at least 48 h later when contractions had ceased compared with women in whom cervical length does not change or decreases. (C) 2021 The Authors. Show less
Khalil, A.; Townsend, R.; Reed, K.; Lopriore, E. 2021
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 ... Show moreObjective 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. (C) 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. Show less
Objective To investigate the prevalence of three additional ultrasound markers, placental dichotomy, cardiomegaly and 'starry-sky' liver, in monochorionic twin pregnancy with twin anemia... Show moreObjective 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. (C) 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Show less
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... Show moreObjectives 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-basedmanagement 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 >= 8g/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 (C) 2019 ISUOG. Published by John Wiley & Sons Ltd. Show less
Objective Congenital heart defects (CHD) are still missed frequently in prenatal screening programs, which can result in severe morbidity or even death. The aim of this study was to evaluate the... Show moreObjective Congenital heart defects (CHD) are still missed frequently in prenatal screening programs, which can result in severe morbidity or even death. The aim of this study was to evaluate the quality of fetal heart images, obtained during the second-trimester standard anomaly scan (SAS) in cases of CHD, to explore factors associated with a missed prenatal diagnosis. Methods In this case-control study, all cases of a fetus born with isolated severe CHD in the Northwestern region of The Netherlands, between 2015 and 2016, were extracted from the PRECOR registry. Severe CHD was defined as need for surgical repair in the first year postpartum. Each cardiac view (four-chamber view (4CV), three-vessel (3V) view and left and right ventricular outflow tract (LVOT, RVOT) views) obtained during the SAS was scored for technical correctness on a scale of 0 to 5 by two fetal echocardiography experts, blinded to the diagnosis of CHD and whether it was detected prenatally. Quality parameters of the cardiac examination were compared between cases in which CHD was detected and those in which it was missed on the SAS. Regression analysis was used to assess the association of sonographer experience and of screening-center experience with the cardiac examination quality score.Results A total of 114 cases of isolated severe CHD at birth were analyzed, of which 58 (50.9%) were missed and 56 (49.1%) were detected on the SAS. The defects comprised transposition of the great arteries (17%), aortic coarctation (16%), tetralogy of Fallot (10%), atrioventricular septal defect (6%), aortic valve stenosis (5%), ventricular septal defect (18%) and other defects (28%). No differences were found in fetal position, obstetric history, maternal age or body mass index (BMI) or gestational age at examination between missed and detected cases. Ninety-two cases had available cardiac images from the SAS. Compared with the detected group, the missed group had significantly lower cardiac examination quality scores (adequate score (>= 12) in 32% vs 64%; P=0.002), rate of proper use of magnification (58% vs 84%; P=0.01) and quality scores for each individual cardiac plane (4CV (2.7 vs 3.9; P<0.001), 3V view (3.0 vs 3.8; P=0.02), LVOT view (1.9 vs 3.3; P<0.001) and RVOT view (1.9 vs 3.3; P<0.001)). In 49% of missed cases, the lack of detection was due to poor adaptational skills resulting in inadequate images in which the CHD was not clearly visible; in 31%, the images showed an abnormality (mainly septal defects and aortic arch anomalies) which had not been recognized at the time of the scan; and, in 20%, the cardiac planes had been obtained properly but showed normal anatomy. Multivariate regression analysis showed that the volume of SAS performed per year by each sonographer was associated significantly with quality score of the cardiac examination.Conclusions A lack of adaptational skills when performing the SAS, as opposed to circumstantial factors such as BMI or fetal position, appears to play an important role in failure to detect CHD prenatally. The quality of the cardiac views was inadequate significantly more often in undetected compared with detected cases. Despite adequate quality of the images, CHD was not recognized in 31% of cases. A high volume of SAS performed by each sonographer in a large ultrasound center contributes significantly to prenatal detection. In 20% of undetected cases, CHD was not visible even though the quality of the images was good. (c) 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. Show less
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... Show moreObjective 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 apriori 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 apriori 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 andmeasures is now required. Copyright (c) 2019 ISUOG. Published by John Wiley & Sons Ltd. Show less
Murgano, D.; Khalil, A.; Prefumo, F.; Mieghem, T. van; Rizzo, G.; Heyborne, K.D.; ... ; D'Antonio, F. 2020
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... Show moreObjectives 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 32weeks' 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 32weeks 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 (c) 2019 ISUOG. Published by John Wiley & Sons Ltd. Show less
Objective Neurodevelopmental delay is frequently encountered in children with a congenital heart defect (CHD). Fetuses with major CHD have a smaller head circumference (HC), irrespective of altered... Show moreObjective Neurodevelopmental delay is frequently encountered in children with a congenital heart defect (CHD). Fetuses with major CHD have a smaller head circumference (HC), irrespective of altered cerebral flow or brain oxygenation. This cohort study compared head growth in cases with isolated vs those with non-isolated CHD to evaluate the effect of additional pathology on head size in these fetuses.Method All CHD cases diagnosed prenatally in the period January 2002-July 2014 were selected from our regional registry, PRECOR. Cases of multiple pregnancy, and those affected by maternal diabetes, severe fetal structural brain anomalies or functional CHD were excluded. Subjects were divided into groups according to whether the CHD was isolated, and the non-isolated group was subdivided into three groups: cases with genetic anomaly, extracardiac malformation or placental pathology. In both isolated and non-isolated CHD groups, CHDs were also grouped according to their potential effect on aortic flow and oxygen saturation. Mean HC Z-scores at 20 weeks and increase or decrease (Delta) ofHCZ-scores over the course of pregnancy were compared between isolated and non-isolated groups, using mixed linear regression models.Results Included were 916 cases of CHD diagnosed prenatally, of which 378 (41.3%) were non-isolated (37 with placental pathology, 217 with genetic anomaly and 124 with extracardiac malformation). At 20 weeks, non-isolated cases had significantly lower HC Z-scores than did isolated cases ( Z-score = -0.70 vs -0.03; P < 0.001) and head growth over the course of pregnancy showed a larger decrease in this group (Delta HC Z-score = -0.03 vs -0.01 per week; P = 0.01). Cases with placental pathology had the lowest HC Z-score at 20 weeks ( Z-score = -1.29) and the largest decrease in head growth (Delta HC Z-score= -0.06 per week). In CHD subjects with a genetic diagnosis (Z-score = -0.73; Delta HC Z-score = -0.04 per week) and in those with an extracardiac malformation (Z-score = -0.49; Delta HC Z-score = -0.02 per week), HC Z-scores were also lower compared with those in subjects with isolated CHD. CHDs that result in low oxygenation or flow to the brain were present more frequently in isolated than in non-isolated cases.Conclusions Smaller HC in fetuses with CHD appears to be associated strongly with additional pathology. Placental pathology and genetic anomaly in particular seem to be important contributors to restricted head growth. This effect appears to be irrespective of altered hemodynamics caused by the CHD. Previously reported smaller HC in CHD should, in our opinion, be attributed to additional pathology. Neurodevelopment studies in infants with CHD should, therefore, always differentiate between isolated and non-isolated cases. (c) 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. Show less
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... Show moreObjectives 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 (C) 2019 ISUOG. Published by John Wiley & Sons Ltd. Show less
Zwiers, C.; Lindenburg, I.T.M.; Klumper, F.J.; Haas, M. de; Oepkes, D.; Kamp, I.L. van 2017
