Screening for Common Fetal Trisomies in Twin Pregnancies : First-Trimester Combined, Cell-Free DNA, or Both?

Objective: To examine the distribution of risks for fetal trisomies after first-trimester combined screening in twins and to investigate different strategies for clinical implementation of cell-free DNA (cfDNA) testing. Methods: We retrospectively analyzed all twin pregnancies undergoing first-trimester combined screening over a 10 years' period. The population was stratified according to various risk cut-offs, and we examined different screening strategies for implementation of cfDNA testing in terms of impact on invasive testing rate, cfDNA test failure rate, and economic costs. Results: We included 572 twin pregnancies: 480 (83.92%) dichorionic and 92 (16.08%) monochorionic. Performing a first-line combined screening and offering cfDNA testing to the group with a risk between 1 in 10 and 1 in 1,000, would lead to an invasive testing rate of 2.45%, and cfDNA testing would be performed in 22.20% of the population. This strategy would be cost-neutral compared to universal combined screening alone. Conclusions: First-trimester combined screening results can be used to stratify twin pregnancies into different risk categories and select those that could be offered cfDNA testing. A contingent screening strategy would substantially decrease the need for invasive testing in twins and it would be cost-neutral compared to combined testing alone

Risk of Fetal Loss After Chorionic Villus Sampling in Twin Pregnancy Derived from Propensity Score Matching Analysis

Objective: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. Methods: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. Results: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. Conclusion: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.info:eu-repo/semantics/publishedVersio

Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study

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

multicenter cohort study

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

Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis.

Objective: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies. Data sources: Searches of PubMed, Embase and the Cochrane library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published and 31 December 2016. Results: In total, 35 relevant studies were identified and these reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome. In the combined total of 1,963 cases of trisomy 21 and 225,032 non-trisomy 21 singleton pregnancies the pooled weighted detection rate (DR) and false positive rate (FPR) were 99.7% (95% CI 99.1-99.9%) and 0.04% (95% CI 0.02-0.08%), respectively. In a total of 560 cases of trisomy 18 and 212,019 unaffected singleton pregnancies the pooled weighted DR and FPR were 98.2% (95% CI 95.5-99.2%) and 0.05% (95% CI 0.03-0.07%). In a total of 119 cases of trisomy 13 and 212,883 unaffected singleton pregnancies the pooled weighted DR and FPR were 99.0% (95% CI 65.8-100%) and 0.04% (95% CI 0.02-0.07%). In a total of 36 cases of monosomy X and 7,677 unaffected singleton pregnancies the pooled weighted DR and FPR were 95.8% (95% CI 70.3-99.5%) and 0.14% (95% CI 0.05-0.38%). In a combined total of 17 cases of sex chromosome abnormalities other than monosomy X and 5,383 unaffected singleton pregnancies the pooled weighted DR and FPR were 100% (95% CI 83.6-100%) and 0.003% (95% CI 0-0.07%). For twin pregnancies, in a total of 24 cases of trisomy 21 and 1,111 unaffected cases the DR was 100% (95% 95.2-100%) and FPR was 0% (95% CI 0-0.003%). Conclusion: Screening by analysis of cfDNA in maternal blood in singleton pregnancies could detect >99% of fetuses with trisomy 21, 98% of trisomy 18 and 99% of trisomy 13 at a combined FPR of 0.13%. The number of reported cases of sex chromosome abnormalities is too small for accurate assessment of performance of screening. In twin pregnancies performance of screening for trisomy 21 is encouraging but the number of cases reported is small.pre-print635 K

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

Objective To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. Methods This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11–13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. Results The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48–1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23–0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95–7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. Conclusion In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.pre-print226 K

Fetal loss after chorionic villus sampling in twin pregnancies

To estimate the chorionic villus sampling (CVS) related risk of fetal loss after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (hCG). This was a multicentre study from eight fetal medicine units in which the leadership were trained at the Harris Birthright research centre for fetal medicine in London and the protocols for screening, invasive testing and pregnancy management are similar. The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation, included 316 dichorionic (DC) and 129 monochorionic (MC) twins that had CVS. Multivariable logistic regression analysis with backward step wise elimination was used to examine whether CVS provided a significant independent contribution in the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including materal age, racial origin, weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥95 percentile, free ß-hCG and PAPP-A MoM. Similarly, within the CVS groups multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needles on the risk of fetal loss. There are four main findings of this study. First, in twin pregnancies undergoing CVS, compared to those that do not have CVS, there is a 2-fold increased risk of fetal loss at <24 weeks' gestation and loss at any stage in pregnancy. Second, the factors providing a significant independent contribution in the prediction of miscarriage or fetal loss in twin pregnancies are increased maternal weight, Black racial origin, monochorionicity and more so monoamnionicity, large intertwin discordance in CRL and high fetal NT and in the case of total fetal loss there is also a contribution from low serum PAPP-A. Third, there is a trend for an increased risk of fetal loss from CVS after adjustment for maternal and pregnancy characteristics but this does not reach statistical significance. Fourth, in the twin pregnancies that had CVS there is no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. The 2-fold increased risk of fetal loss following CVS in twin pregnancies can to a great extent be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.

Perinatal outcomes of monochorionic triplet pregnancies: multicenter cohort study.

OBJECTIVE: Monochorionic triplet pregnancies are extremely rare and information on these pregnancies and their complications are limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcomes, and the timing and methods of fetal intervention in monochorionic triplet pregnancies. METHODS: This was a multicenter retrospective cohort study including monochorionic triamniotic (MCTA) triplet pregnancies. The exclusion criteria were twins, or multiple pregnancies with higher order than triplets (e.g. quadruplets, quintuplets), and dichorionic or trichorionic triplet pregnancies. 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 syndrome (TAPS), twin reversed arterial perfusion sequence (TRAP), or selective fetal growth restriction (sFGR) were ascertained from the patient records. Data on antenatal interventions were collected, including selective (fetal) reduction (3 to 2 or 3 to 1), laser surgery, or any active fetal intervention (including amniodrainage). Finally, perinatal outcomes included livebirth, intrauterine demise (IUD), neonatal death (NND), perinatal death (PND) and termination of pregnancy (TOP). Neonatal data such as GA at birth, birthweight, neonatal intensive care unit (NICU) admission, and neonatal morbidity were also collected. RESULTS: In our cohort of MCTA triplet pregnancies (n=153 after excluding early miscarriages, TOP and loss to follow-up), the majority (90%) were managed expectantly. The incidence of fetal abnormalities and TRAP was 13.7% and 5.2%, respectively. The most common antenatal complication related to chorionicity was TTTS, which complicated just over a quarter (27.6%) of the pregnancies, followed by sFGR (16.4%), while TAPS (both spontaneous and post-laser) occurred in only 3.3%; no antenatal complication was recorded in 49.3% of pregnancies. Survival was largely associated with the development of these complications: 85.1%, 100% and 47.6% of pregnancies had at least one surviving newborn in those without antenatal complications, complicated by sFGR, or complicated by TTTS, respectively. The overall rates of preterm birth prior to 28 weeks and prior to 32 weeks' gestation were 14.5% and 49.2%, respectively. CONCLUSION: MCTA triplet pregnancies represent a challenge in counseling, surveillance and management as monochorionicity-related complications occur in almost half of these pregnancies, which negatively impact their perinatal outcomes. This article is protected by copyright. All rights reserved