The heart after surviving twin-to-twin transfusion syndrome.

BACKGROUND: The persistent changes in cardiac structure and function in children who survived twin-to-twin transfusion syndrome remain a matter of concern and controversy. Current fetal echocardiographic parameters and their postnatal evolution can help improve our understanding of the subject. OBJECTIVE: To describe the echocardiographic changes of monochorionic fetuses affected by twin-to-twin transfusion syndrome, the recipient and the donor, before and after laser photocoagulation and to determine their evolution in the third trimester and during their first year of life. STUDY DESIGN: An observational study was conducted including 55 uncomplicated monochorionic diamniotic twins and 78 pairs with twin-to-twin transfusion syndrome, 44 stage I-II and 34 stage III-IV, prospectively enrolled from 2015 until 2018. Comprehensive echocardiography was performed at 4 time periods: before laser photocoagulation, at 24 to 72 hours after surgery, at 28 to 30 weeks of gestation, and at 6 to 12 months after birth. Echocardiographic parameters were transformed to z-scores or indexed for heart area, estimated fetal weight, or body mass surface. RESULTS: At diagnosis, recipients in all stages presented larger hearts (cardiothoracic ratio z-score: 2.77 [0.8] vs controls: -0.03 [0.5]; P<.001) and signs of ventricular hypertrophy (left end-diastolic ventricle wall thickness: 2.68 [0.7] vs controls -0.03 [0.7]; P<.001), along with systolic (cardiac index recipients: 317 [114] mL/min/kg vs controls: 400 [120] mL/min/kg, P<.001) and diastolic impairment (isovolumetric relaxation time z-score: 2.76 [0.6] vs controls: 0.05 [0.6]; P<.001). Donors presented smaller ventricular areas and diameters when compared with controls (left end-diastolic ventricle area z-score: -1.48 [1] vs 0.03 [0.9]; P<.001), along with decreased longitudinal motion (tricuspid annular plane systolic excursion z-score: -0.9 [1] vs controls -0.04 [1]; P<.001) and shorter ejection time z-score (-1.5 [0.7] vs controls: 0.0 [0.7]; P<.001). After surgery, an improvement in functional parameters was observed in both fetuses, whereas most morphometric changes prevailed in donors and recipients in the prenatal period. Postnatally, cardiac remodeling persisted in recipients (left relative wall thickness: 0.34 [0.02] vs controls: 0.30 [0.02]; P<.001), whereas donors mainly presented a decreased longitudinal motion in infancy (tricuspid annular plane systolic excursion z-score: -0.72 [0.7] vs controls: 0.23 [0.9]; P<.05). CONCLUSION: Cardiac remodeling is present in both fetuses at the twin-to-twin transfusion syndrome diagnosis, whereas diastolic dysfunction is only significant in the recipient. Fetal therapy improves most echocardiographic parameters, although postnatally, the echocardiographic changes persist in both fetuses.

Impact of Preoperative Cervical Length on Pregnancy Outcome in Twin-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the impact of preoperative cervical length on pregnancy outcome in monochorionic diamniotic twin pregnancies complicated by twin-twin transfusion syndrome that underwent laser surgery or cord occlusion. MATERIALS AND METHODS: Retrospective study of 330 patients stratified by preoperative cervical length (≥25 mm, 16-24 mm,≤15 mm). Maternal characteristics, operative data, and pregnancy outcomes were compared between the cervical length groups as well as between the subgroups of patients with a cervical length≤15 mm according to management (expectant vs. cerclage). RESULTS: A preoperative cervical length≥25 mm was observed in 82% (n=271) of cases, 16-24 mm in 9% (n=29), and≤15 mm in 9% (n=30). Patients with a preoperative cervical length≤15 mm showed shorter median procedure-to-delivery interval (5.5 weeks vs. 11.6 (16-24 mm) vs. 13.0 (≥25 mm); p<0.001); lower median gestational age at delivery (29.5 weeks vs. 34.3 (16-24 mm) vs. 33.4 (≥25 mm); p<0.001); higher rate of preterm delivery<32 weeks (78 vs. 20% (16-24 mm) vs. 31% (≥25 mm); p<0.001); and lower neonatal survival rate of at least one twin (70 vs. 88% (16-24 mm) vs. 93% (≥25 mm); p<0.001). Outcome of patients with a preoperative cervical length≤15 mm was similar regardless of management. CONCLUSION: Monochorionic diamniotic twin pregnancies complicated by twin-twin transfusion syndrome with a preoperative cervical length≤15 mm showed a higher rate of preterm delivery<32 weeks and lower neonatal survival. The role of a cervical cerclage remains unclear.

Prescriptive standards of echocardiographic morphometric and functional parameters in uncomplicated monochorionic diamniotic fetuses.

OBJECTIVE: To create prescriptive standards of cardiac morphometric and functional parameters in a cohort of uncomplicated monochorionic diamniotic (MCDA) twins. METHOD: Fetal echocardiography was performed in a cohort of uncomplicated monochorionic twin fetuses scanned longitudinally, including comprehensive morphometric and functional parameters, using 2-D imaging, M-mode and conventional Doppler. A multilevel polynomial hierarchical model adjusted by gestational age and estimated fetal weight was used to fit each cardiac parameter. RESULTS: The global heart dimensions including the atrial and ventricular areas, the ventricles dimensions and myocardial wall thicknesses and most of the functional parameters, such as the longitudinal myocardial motion and the biventricular cardiac output showed a positive quadratic increment throughout pregnancy. On the other hand, the left ejection fraction, shortening fraction and right fractional area change decreased with gestational age. Scatterplots for the main structural and functional parameters and ratios by gestational age, with mean, 5th, 10th, 90th, and 95th percentiles are provided. Regression equations by estimated fetal weight are also created. CONCLUSION: We provide specific comprehensive echocardiographic prescriptive standards for uncomplicated MCDA twin fetuses following current standardized methodology. The implementation of these charts will potentially help to better identify abnormal cardiovascular parameters associated to monochorionic complications.

Left myocardial performance index in monochorionic diamniotic twin pairs complicated by selective fetal growth restriction with abnormal umbilical artery Doppler.

OBJECTIVE: To evaluate left myocardial performance index (MPI) and its time intervals in monochorionic diamniotic (MCDA) twin pairs complicated by selective fetal growth restriction (sFGR) with abnormal (persistent -type II- or intermittent -type III- absent or reversed end-diastolic flow) umbilical artery Doppler. METHODS: Retrospective study including 16 MCDA twin pairs with sFGR type II, 26 MCDA twin pairs with sFGR type III and 42 gestational age-matched uncomplicated MCDA twin pairs in a single tertiary center. Left isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured and MPI calculated by conventional Doppler at diagnosis of sFGR. RESULTS: In sFGR type II, the smaller twin had shorter ET and prolonged IRT and MPI, while the larger twin showed prolonged ICT and MPI as compared to uncomplicated MCDA twins. In sFGR type III, the smaller twin had shorter ICT and ET, while the larger twin showed prolonged ICT, IRT, and MPI in comparison to controls. CONCLUSION: A differential pattern of MPI time intervals could be observed in MCDA twins with sFGR type II and III. All twins had echocardiographic signs of pressure/volume overload, except the smaller twin type III with shorter systolic times probably reflecting reduced volume load.

Perinatal outcome after selective termination in dichorionic twins discordant for congenital anomalies.

INTRODUCTION: Our objective was to evaluate the perinatal outcome of selective termination of dichorionic twin pregnancies with discordant anomalies, according to gestational age at time of procedure. MATERIAL AND METHODS: Retrospective review of 147 dichorionic twin pregnancies referred to our Fetal Medicine Unit between 2003 and 2018 for selective termination. Gestational age at delivery, fetal loss, and overall and 28-day post-delivery survival rates, were evaluated according to gestational age at time of procedure. Selective termination procedure was defined as early, intermediate, and late when performed before 18 weeks, between 18 and 23 weeks, and after 23 weeks, respectively. Kruskal-Wallis and chi-squared test were used to compare groups. RESULTS: Overall survival at 28 days post-delivery, pregnancy loss, and preterm delivery before 32 weeks of gestation rates were 93.4%, 6.9%, and 15.5%, respectively. When stratified by gestational age at procedure, intermediate selective termination was associated with a lower survival rate than early and late procedures (86% vs. 96.9% and 100%, respectively; p = 0.035), and a nonsignificant trend for higher pregnancy loss (12% vs. 3.1%). Preterm delivery before 32 weeks of gestation occurred in 27% of late procedures, which was significantly higher than in early (9.5%) and intermediate (18.2%) procedures. CONCLUSIONS: Selective termination in dichorionic twin pregnancies with discordant fetal anomaly is associated with low pregnancy loss and preterm delivery rate, primarily when performed before 18 weeks. When legally possible, late procedures can be a good alternative, particularly in those cases diagnosed beyond the 18th week of gestation.

Risk Factors Associated with Preterm Prelabor Rupture of Membranes after Cord Occlusion in Monochorionic Diamniotic Twins.

INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) is a common complication after fetal surgeries. The aim of this study was to assess risk factors for and outcomes after PPROM following cord occlusion (CO) in monochorionic diamniotic (MCDA) pregnancies. METHODS: This was a retrospective cohort study of 188 consecutive MCDA pregnancies treated by bipolar or laser CO, either primarily because of discordant malformation (dMF) or severe selective fetal growth restriction (sFGR), or secondarily when complete bichorionization was not possible in case of twin-to-twin transfusion syndrome (TTTS) or sFGR. Intentional septostomy was performed when needed. The procedure-related PPROM was defined as rupture of membranes <32 weeks' gestation (PROM <32 weeks). Selected pre-, intra-, and early postoperative variables were analyzed by univariate and binomial logistic regression to determine they are correlated to PROM <32 weeks after CO. RESULTS: Between 2006 and 2017, 188 cases underwent CO. Diagnosis was TTTS in 28.2% (n = 53), severe sFGR in 49.5% (n = 93), and dMF in 22.3% (n = 42). PROM <32 weeks occurred in 21.3% (n = 40), resulting in worse perinatal outcomes, as preterm birth <32 weeks occurred in 80.7% (vs. 8.3%, p = 0.000), procedure-to-delivery interval was 47.5 days (vs. 125, p = 0.000), gestational age (GA) at birth 30.0 weeks (vs. 37.7 weeks, p = 0.000), and survival 65.0% (vs. 91.1%, p = 0.000). In univariate analysis, indication, anterior placenta, cervical length, GA at surgery, operation time, amniodistention and drainage fluid volumes, chorioamniotic membrane separation, and septostomy were selected as relevant factors to be included in the regression model. In a multivariate analysis, TTTS was the only factor associated to PROM <32 weeks (OR 3.5 CI 95% 1.5-7.9). CONCLUSIONS: PROM <32 weeks after CO increases the risk of preterm delivery. In this cohort, the membrane rupture was more likely when CO was done in the context of TTTS.

Prediction of Perinatal Mortality in Ebstein's Anomaly Diagnosed in the Second Trimester of Pregnancy.

OBJECTIVES: Firstly, to describe the outcome of a series of fetuses with Ebstein's anomaly (EA) and, secondly, to study the utility of different second-trimester echocardiographic parameters to predict fetal and neonatal mortality. METHODS: 39 fetuses with EA diagnosed between 18 and 28 weeks of gestation were included. Fetal echocardiography included the cardiothoracic ratio (CTR); right atrial (RA) area index; displacement of the tricuspid valve (TV); tricuspid regurgitation; pulmonary artery; and ductus arteriosus flow characteristics. Additionally, 2 novel parameters were obtained: the relative RA area ratio (RA area/cardiac area) and the TV displacement index (TVDI, TV displacement distance/longi-tudinal diameter of the left ventricle). Correlation between the echocardiographic variables and the primary outcome of perinatal mortality or survival at 1 year of life was evaluated. RESULTS: From the initial cohort, 8 cases were excluded due to complex congenital heart defects. Termination of pregnancy (TOP) was performed in 15 cases, and fetal death was diagnosed in 3 cases. In the live-born cohort of 13 patients, 4 died in the neonatal period, yielding a perinatal survival rate of 29 and 56%, respectively, after excluding TOP cases. Compared with survivors, nonsurvivors showed a significantly higher CTR (56.7 ± 16.2 vs. 42.6 ± 8.6; p = 0.04), relative RA area ratio (0.39 ± 0.13 vs. 0.25 ± 0.05; p = 0.01), and TVDI (0.62 ± 0.17 vs. 0.44 ± 0.12; p = 0.03) at diagnosis. The best model to predict perinatal mortality was obtained by using a scoring system which included the relative RA area ratio and TVDI (AUC 0.905 [95% CI 0.732-1.000]). CONCLUSIONS: Fetuses with a relative RA area ratio ≥0.29 and TVDI ≥0.65 at the second trimester have the highest risk of dying in the perinatal stage.

Gender-Specific Antenatal Growth Reference Charts in Monochorionic Twins.

OBJECTIVE: To create antenatal gender-specific reference growth charts in uncomplicated monochorionic diamniotic twins. MATERIALS AND METHODS: This is a prospective longitudinal study in which uncomplicated monochorionic (MC) twin pregnancies were included from 23 + 4 weeks of gestation onwards. Estimated fetal weight (EFW) and biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) were evaluated in both fetuses every 2 weeks using standardized methodology. Maternal and fetal complications were excluded. Charts were fitted for each biometric parameter and EFW in relation to gestational age and fetal gender using multilevel mixed models. RESULTS: The final analysis included a total of 456 ultrasound examinations in 62 MC twins, with a mean of 7 scans per pregnancy (range 5-8). The mean as well as 5th and 95th percentiles of each biometric parameter and EFW were adjusted in relation to gender and gestational age between 24 and 37 weeks of gestation. Male fetuses have higher reference values than females, and the disparity is larger in the upper centiles of the distribution. DISCUSSION: We provide gender-specific reference growth charts for MC twins. We suggest that these charts will improve prenatal MC twin assessment and surveillance, with a more accurate classification of normal or growth-restricted fetuses adjusted per sex.

Differential Changes in Myocardial Performance Index and Its Time Intervals in Donors and Recipients of Twin-to-Twin Transfusion Syndrome before and after Laser Therapy.

OBJECTIVE: To evaluate left myocardial performance index (MPI) and time intervals in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser surgery. METHODS: Fifty-one fetal pairs with TTTS and 47 uncomplicated monochorionic twin pairs were included. Left ventricular isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured using conventional Doppler. RESULTS: Recipients showed prolonged ICT (46 ± 12 vs. 31 ± 8 vs. 30 ± 5 ms; p < 0.001) and IRT (51 ± 9 vs. 43 ± 8 vs. 43 ± 5 ms; p < 0.001) and higher MPI (0.57 ± 0.12 vs. 0.47 ± 0.09 vs. 0.44 ± 0.05; p < 0.001) than donors and controls. Donors showed shorter ET than recipients and controls (157 ± 12 vs. 169 ± 10 vs. 168 ± 10 ms; p < 0.001) and higher MPI than controls (0.47 ± 0.09 vs. 0.44 ± 0.05; p = 0.006). Preoperative MPI changes were observed in all TTTS stages. Time intervals partially improved after surgery. CONCLUSION: Donor and recipient twins had higher MPI due to different changes in the time intervals, possibly reflecting the state of hypovolemia in the donor and hypervolemia and pressure overload in the recipient.

Rate and Outcomes of Pulmonary Stenosis and Functional Pulmonary Atresia in Recipient Twins with Twin-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the rate of pulmonary stenosis and functional pulmonary atresia (PS/PA) in recipient twins prior to fetal surgery for twin-twin transfusion syndrome (TTTS) and their pre- and postnatal outcomes. METHODS: We carried out a prospective study including 260 cases of TTTS. Echocardiography was performed before laser surgery to detect the presence of PS/PA. The outcomes of recipients with and without PS/PA were compared. The need of postnatal cardiac interventions and the survival rate at 6 months of age were also evaluated. RESULTS: PS was observed in 16/260 (6.2%) of recipient twins and PA in 12/260 (4.6%). After fetal surgery, 10/28 (35.7%) recipients died, 9/28 (32.1%) showed in utero regression, and 9/28 (32.1%) had persistence of PS/PA. Postnatally, seven recipients underwent percutaneous balloon pulmonary valvuloplasty, one required surgical valvotomy and one palliative surgery. Pregnancies with recipient twins with PS/PA had lower survival of at least one twin (67.9 vs. 83.6%, p = 0.045) and lower overall survival (57.1 vs. 72.8%, p = 0.015) at 6 months of age. CONCLUSION: PS and PA were observed in 10.8% of recipients. Among these, about one third showed persistence of pulmonary valve pathology after delivery, which stresses the need for strict follow-up.

Fetal Aortic Valvuloplasty: Experience and Results of Two Tertiary Centers in Spain.

OBJECTIVE: Fetal aortic valvuloplasty (FAV) may avoid progression of critical aortic stenosis (CAS) to hypoplastic left ventricle, improving the options for biventricular circulation (BVC). We describe the results of FAV in 2 referral centers in Spain. METHODS: We analyzed all FAVs performed in the period 2007-2015. The selection of candidates, the technique, and postnatal management were made following an agreed protocol. A descriptive analysis of survival, type of circulation after birth, and complications was made, considering all deaths in the first 48 h after FAV as FAV-related. RESULTS: FAV was performed in 28 fetuses at a median gestational age (GA) of 23 weeks (range, 20-32). FAV was technically successful in 22 (78.6%), of whom 11 were born alive and with intention to treat. Eight (72.7%) resulted in BVC and 3 (27.3%) in univentricular circulation. The rate of FAV-related deaths was 32%. These patients underwent FAV earlier than live-born fetuses (median GA at FAV 22 weeks [range, 20.0-25.0] vs. 24.5 weeks [range, 21.0-32.0], respectively, p = 0.031). CONCLUSIONS: A significant proportion of fetuses with CAS who undergo technically successful FAV have BVC postnatally. However, FAV implies a high risk of fetal death, which highly depends on the GA at which this intervention is required.

Cord Occlusion in Monochorionic Twins with Early Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler: A Consecutive Series of 90 Cases.

OBJECTIVE: To describe perinatal outcomes achieved with cord occlusion (CO) in monochorionic twins with severe selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler in the IUGR twin (types II and III). METHODS: We studied a consecutive series of 90 cases of sIUGR with abnormal Doppler treated with CO of the IUGR fetus. Abnormal Doppler was defined as continuous (type II, n = 41) or intermittent (type III, n = 49) absent/reversed end-diastolic flow. All cases presented at least one of the following severity criteria: gestational age (GA) <22 weeks, inter-twin estimated weight discordance >35%, reversed end-diastolic umbilical artery flow or ductus venosus pulsatility index >95th centile. We prospectively recorded pregnancy course and perinatal outcome. RESULTS: Median GA at surgery was 20.6 weeks and mean duration 22.4 min. Miscarriage (<24 weeks) occurred in 3.3% (3/90) and preterm delivery <32 weeks in 7.1% (6/84) of continuing pregnancies. GA at delivery was 36.4 weeks and neonatal survival of the larger twin was achieved in 93.3%. CONCLUSION: In a consecutive series studied by an experienced team, CO in monochorionic twins with severe sIUGR type II or III was associated with delivery >32 weeks in 92.9% and neonatal survival of the normal twin in 93.3% of pregnancies.

Severity of Fetal Brain Abnormalities in Congenital Heart Disease in Relation to the Main Expected Pattern of in utero Brain Blood Supply.

OBJECTIVES: We evaluated the hypothesis that in fetuses with congenital heart disease (CHD) there is a correlation between the expected pattern of in utero brain blood supply and the severity of neurodevelopmental impairment. METHODS: A total of 58 fetuses with CHD and 58 controls underwent a Doppler ultrasound and fetal MRI at 36-38 weeks. Fetuses with CHD were divided into two functional classes: class A with an expected severe reduction in oxygenated brain blood supply (left outflow tract obstruction and transposition of great vessels) and class B with theoretically near-normal or mildly impaired oxygenated brain blood supply (other CHD). Head biometry and cerebroplacental Doppler were assessed by ultrasound, and brain volumetry, cortical development and metabolism by MRI. RESULTS: Both class A and B CHD fetuses had significant differences in head biometry, brain perfusion, cortical development and brain metabolism compared with controls. However, there was a significant linear tendency for head biometry, cerebral Doppler, volumes, cortical sulcation and metabolic ratios across the three clinical groups, with signs of more severe brain alterations in type A CHD fetuses. CONCLUSIONS: All fetuses with CHD showed significant brain developmental changes, but differences were more pronounced in CHD associated with an expected severe reduction in oxygenated blood supply to the brain.

Accuracy of Fetal Echocardiography in the Differential Diagnosis between Truncus Arteriosus and Pulmonary Atresia with Ventricular Septal Defect.

OBJECTIVES: To report on the accuracy of fetal echocardiography in the distinction between truncus arteriosus communis (CAT) and pulmonary atresia with ventricular septal defect (PA-VSD) and to describe the association with extracardiac and chromosomal anomalies. METHODS: This was a retrospective study on 31 fetuses with a single arterial trunk overriding a VSD with a nonidentifiable right ventricle outflow tract with anterograde flow. Data on the type of cardiac defect, gestational age, characteristics of the arterial trunk valve, presence of additional vascular, chromosomal and extracardiac abnormalities and postnatal outcome were obtained. Misdiagnosed cases were reevaluated by four-dimensional spatiotemporal image correlation (4D-STIC) echocardiography. RESULTS: The overall diagnostic accuracy was 81% and increased to 93.5% with 4D-STIC. Chromosomal and extracardiac anomalies were detected in 40 and 27%, respectively. In the PA-VSD group, patent ductus arteriosus and major aortopulmonary collateral arteries (MAPCAs) were present in 70 and 50% of the cases, respectively, coexisting in 1 of 5 cases. MAPCAs were significantly associated with a right aortic arch and with a 22q11 microdeletion in 50% of cases. CONCLUSIONS: A prenatal distinction between CAT and PA-VSD can currently be achieved in most cases. MAPCAs should be actively searched for when PA-VSD is suspected, as they are associated with a higher risk of 22q11 microdeletion and potentially complicate postnatal treatment.

Longitudinal annular displacement by M-mode (MAPSE and TAPSE) in twin-to-twin transfusion syndrome before and after laser surgery.

OBJECTIVE: To evaluate mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE) in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser therapy. METHODS: A prospective study in 24 fetal pairs with TTTS evaluated 24 h before and within 48 h after fetoscopy and 13 gestational age-matched normal monochorionic fetal pairs. MAPSE and TAPSE were measured in an apical or basal four-chamber view by placing the M-mode cursor at the lateral valve ring. RESULTS: Mean preoperative MAPSE (controls 3.6 ± 1.3 mm vs. donors 2.7 ± 0.8 mm vs. recipients 2.8 mm ± 0.9; P < 0.001) and TAPSE (controls 4.4 ± 1.5 mm vs. donors 3.3 ± 1 mm vs. recipients 3.6 ± 1.1 mm; P < 0.001) values were significantly reduced in both TTTS fetuses. When subdividing according to TTTS stages, changes were significant in both stage I-II and III-IV subgroups, although differences were more pronounced in the latter. All observations remained unchanged 48 h post-fetoscopy. CONCLUSION: Both recipient and donor fetuses had decreased global longitudinal motion, even in early TTTS stages.

Antral follicle count as a marker of ovarian biological age to reflect the background risk of fetal aneuploidy.

STUDY QUESTION: Can antral follicle count (AFC) measured during pregnancy be used as a marker of ovarian age to assess the background risk of fetal aneuploidy? SUMMARY ANSWER: AFC was lower than expected according to maternal chronological age in trisomic pregnancies; therefore ovarian age could potentially reflect a more precise background risk of fetal aneuploidy screening. WHAT IS KNOWN ALREADY: The decline in a woman's reproductive function is determined by a decline in the ovarian follicle pool and the quality of oocytes. The quantitative status of ovarian reserve can be indirectly assessed by AFC, but the role of AFC as an aneuploidy risk marker in pregnant women has not been assessed yet. STUDY DESIGN, SIZE, DURATION: Our study comprised a prospective cohort including 1239 singleton pregnancies scanned before 14 weeks in our center during a 14-month period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reference ranges for AFC were constructed using 812 spontaneously conceived, chromosomally normal singleton ongoing pregnancies using the Lambda-Mu-Sigma method. The study population (n = 934) included 19 pregnancies with viable autosomal trisomies (trisomies 21, 18 and 13), 17 non-viable autosomal trisomies (other than 21, 18 or 13), 7 monosomies X, 1 sex trisomy and 3 triploidies (total n = 47 with chromosomal abnormalities). AFC in chromosomally abnormal pregnancies was plotted against the reference ranges. AFC multiple of the median was calculated according to the median AFC obtained by each year of age. MAIN RESULTS AND THE ROLE OF CHANCE: Sixty-eight percent of women carrying a pregnancy with viable trisomies and 65% with non-viable trisomies presented an AFC below the 50th percentile. The median ovarian age in viable trisomies and non-viable trisomies was estimated to be 3 and 6 years above than median maternal age, respectively. However, the median ovarian age in monosomies X and triploidies was not higher than median maternal age. LIMITATIONS, REASONS FOR CAUTION: We did not assess the intra- and inter-observer reliability, or use specific three-dimensional analysis which may have advantages over our two-dimensional study. In clinical practice, a drawback for assessing AFC during pregnancy is that transvaginal ultrasound is needed at the 11- to 13-week scan, when the transabdominal approach is used most commonly. Furthermore identifying ovaries by ultrasound during pregnancy could be challenging. WIDER IMPLICATIONS OF THE FINDINGS: Considering that AFC reflects ovarian aging, this 'ovarian biological age' could potentially reflect a more precise background risk of fetal aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by PI 11/00685. Instituto de Salud Carlos III. Fondo de Investigación Sanitaria. No competing interests declared.

Collaborative study of 4-dimensional fetal echocardiography in the first trimester of pregnancy.

OBJECTIVES: Accumulating evidence supports a role for 2-dimensional fetal echocardiography in the first trimester of pregnancy for the identification of congenital heart defects. Our objective was to investigate the role of 4-dimensional (4D) sonography in the identification of congenital heart defects between 11 and 15 weeks of pregnancy. METHODS: This study included 4 centers with expertise in first-trimester 4D fetal echocardiography. Fetuses with and without confirmed heart defects were evaluated between 11 and 15 weeks and their volume data sets were uploaded onto a centralized file transfer protocol server. RESULTS: Forty-eight volume data sets from fetuses with normal (n = 17) and abnormal (n = 16) hearts were evaluated. Overall, the median (range) accuracy, sensitivity, and specificity, as well as the positive and negative likelihood ratios, for the identification of fetuses with congenital heart defects were 79% (77%-83%), 90% (70%-96%), 59% (58%-93%), 2.35 (2.05-9.80), and 0.18 (0.08-0.32), respectively. CONCLUSIONS: (1) Four-dimensional fetal echocardiography can be performed in the first and early second trimesters of pregnancy; and (2) 4D volume data sets obtained from fetuses between 11 and 15 weeks can be remotely acquired and accurately interpreted by different centers.

Preterm Prelabour Rupture of Membranes before Viability in Twin Pregnancies: What Can We Expect?

Preterm prelabour rupture of membranes (PPROMs) before viability carries significant perinatal mortality and morbidity. Clinical management and prenatal counselling are a challenge, especially in twin pregnancies, due to scarce evidence on how previable PPROM affects this population. The aim of this study was to describe pregnancy outcomes of twin pregnancies complicated with previable PPROM and evaluate potential prognostic factors that may predict perinatal mortality. A retrospective cohort including dichorionic and monochorionic diamniotic twin pregnancies complicated with PPROM before 24 + 0 weeks of pregnancy was evaluated. Perinatal outcomes of pregnancies managed expectantly were described. Factors predicting perinatal mortality or reaching periviability (defined from 23 + 0 weeks onwards) were evaluated. Of the 45 patients included, 7 (15.6%) spontaneously delivered within the first 24 h after diagnosis. Two patients (5.3%) requested selective termination of the affected twin. In the 36 ongoing pregnancies that opted for expectant management, the overall survival rate was 35/72 (48.6%). There were 25/36 (69.4%) patients who delivered after 23 + 0 weeks of pregnancy. When periviability was achieved, neonatal survival increased up to 35/44 (79.5%). Gestational age at delivery was the only independent risk factor of perinatal mortality. The overall survival rate of twin pregnancies complicated with previable PPROM is poor but similar to singletons. No prognostic factors, apart from achieving periviability, were identified as individual predictors of perinatal mortality.

Cord blood cardiovascular biomarkers in tetralogy of fallot and D-transposition of great arteries.

Previous reports suggest that cord blood biomarkers could serve as a prognostic tool for conotruncal congenital heart defects (CHD). We aimed to describe the cord blood profile of different cardiovascular biomarkers in a prospective series of fetuses with tetralogy of Fallot (ToF) and D-transposition of great arteries (D-TGA) and to explore their correlation with fetal echocardiography and perinatal outcome. Methods: A prospective cohort study (2014-2019), including fetuses with isolated ToF and D-TGA and healthy controls, was conducted at two tertiary referral centers for CHD in Barcelona. Obstetric ultrasound and fetal echocardiography were performed in the third trimester and cord blood was obtained at delivery. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factorß (TGFß), placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. Results: Thirty-four fetuses with conotruncal-CHD (22 ToF and 12 D-TGA) and 36 controls were included. ToF-fetuses showed markedly increased cord blood TGFß (24.9 ng/ml (15.6-45.3) vs. normal heart 15.7 ng/ml (7.2-24.3) vs. D-TGA 12.6 ng/ml (8.7-37.9); P = 0.012). These results remained statistically significant even after adjusting for maternal body mass index, birth weight and mode of delivery. TGFß levels showed a negative correlation with the pulmonary valve diameter z-score at fetal echocardiography (r = -0.576, P = 0.039). No other differences were found in the rest of cord blood biomarkers among the study populations. Likewise, no other significant correlations were identified between cardiovascular biomarkers, fetal echocardiography and perinatal outcome. Conclusions: This study newly describes increased cord blood TGFß concentrations in ToF compared to D-TGA and normal fetuses. We also demonstrate that TGFß levels correlate with the severity of right ventricle outflow obstruction. These novel findings open a window of research opportunities on new prognostic and potential preventive strategies.

Latency to delivery in physical examination-indicated cerclage in twins is similar to that in singleton pregnancies.

OBJECTIVE: To compare latency to delivery and perinatal outcomes between twin and singleton pregnancies undergoing physical examination-indicated cerclage. METHODS: Retrospective observational study (2007-2017) of women who underwent physical examination-indicated cerclage at the Hospital Clinic of Barcelona. Primary outcomes were latency from cerclage to delivery and gestational age at delivery. Secondary outcomes included: neonatal morbidity and mortality, preterm prelabor rupture of membranes, clinical chorioamnionitis and cerclage displacement. Wilcoxon-test and χ2 test were used to compare continuous and categorical variables. RESULTS: Sixty women were included (17 twins and 43 singletons). There were no differences in gestational age at cerclage or presence of bulging membranes between groups. Median (25th;75th percentile) gestational age at delivery was 27.1 (24.5;32.3) weeks in the twin group and 27.6 (25.3;35.3) weeks in the singleton group (P = 0.594). There were no statistically significant differences in latency from cervical cerclage to delivery between the two groups (43 days [21;64] vs. 29 days [16;76], respectively; P = 0.938). There were no differences in neonatal mortality (2/26 [7.7%] vs. 1/33 [3.1%]; P = 0.578) or in composite neonatal morbidity (14 [53.9%] vs. 14 [42.4%]; P = 0.283) between groups, respectively. CONCLUSION: These results suggest that physical examination-indicated cerclage placement in twins could prolong latency to delivery similarly to singleton pregnancies.