Publications by authors named "Mar Bennasar"

25 Publications

  • Page 1 of 1

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

Prenat Diagn 2021 Jun 27. Epub 2021 Jun 27.

Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Barcelona, Spain.

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.
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http://dx.doi.org/10.1002/pd.5999DOI Listing
June 2021

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

Fetal Diagn Ther 2021 15;48(6):457-463. Epub 2021 Jun 15.

BCNatal Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1159/000516513DOI Listing
June 2021

Uncomplicated Monochorionic Twins: Two Normal Hearts Sharing One Placenta.

J Clin Med 2020 Nov 9;9(11). Epub 2020 Nov 9.

Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), 08028 Barcelona, Spain.

Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography was performed at 26-30 weeks gestation and cord blood B-type natriuretic peptide (BNP) was measured at delivery. In both groups, z-scores for echocardiographic parameters were within normal ranges; however the monochorionic group had larger atrial areas (mean (standard deviation) right atria-to-heart ratio: 17.0 (2) vs. 15.9 (1); = 0.018; left atria-to-heart ratio: 17.0 (3) vs. 15.8 (2); < 0.001) and signs of concentric hypertrophy (right relative wall thickness: 0.66 (0.12) vs. 0.56 (0.11); < 0.001; left relative wall thickness: 0.69 (0.14) vs. 0.58 (0.12); < 0.001). Longitudinal function was increased in twins, leading to higher tricuspid annular plane systolic excursion (6.9 mm (0.9) vs. 5.9 mm (0.7); < 0.001) and mitral annular plane systolic excursion (4.9 mm (0.8) vs. 4.4 mm (1.1); < 0.001. BNP levels at birth were also higher in MCDA twins (median [interquartile range]: 20.81 pg/mL [16.69-34.01] vs. 13.14 pg/mL [9.17-19.84]; < 0.001). Thus, uncomplicated MCDA fetuses have normal cardiac shape and function, but signs of cardiac adaptation were identified by echocardiographic and biochemical parameters, when compared with singletons.
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http://dx.doi.org/10.3390/jcm9113602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695261PMC
November 2020

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

Fetal Diagn Ther 2020 4;47(8):604-614. Epub 2020 Feb 4.

Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Complutense University of Madrid, Madrid, Spain.

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.
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http://dx.doi.org/10.1159/000504979DOI Listing
June 2021

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.

Fetal Diagn Ther 2018 19;44(4):305-310. Epub 2018 Jan 19.

BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.

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.
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http://dx.doi.org/10.1159/000485380DOI Listing
March 2019

Gender-Specific Antenatal Growth Reference Charts in Monochorionic Twins.

Fetal Diagn Ther 2018 21;44(3):202-209. Epub 2017 Dec 21.

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.
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http://dx.doi.org/10.1159/000484555DOI Listing
January 2019

Selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies.

Semin Fetal Neonatal Med 2017 12 20;22(6):376-382. Epub 2017 May 20.

Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecologia, Obstetricia i Neonatologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain. Electronic address:

Selective intrauterine growth restriction (sIUGR) affects 10-15% of all monochorionic pregnancies. Early severe forms are associated with intrauterine demise or neurological adverse outcome for both twins. The characteristics of umbilical artery (UA) Doppler in the IUGR fetus determine three clinical types: (I) normal UA Doppler and associated with good prognosis; (II) persistently absent/reverse UA end-diastolic flow and associated with early deterioration of the IUGR twin and very preterm delivery; (III) intermittently absent/reverse end-diastolic flow in the UA, and associated with unexpected fetal demise or neurological injury in one or both twins. Types II and III pose important challenges for management. Placental laser or cord occlusions do not seem to increase survival, but they might improve the outcomes of the larger twin. The use of an algorithm with severity criteria may help in counseling and planning management.
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http://dx.doi.org/10.1016/j.siny.2017.05.001DOI Listing
December 2017

Online versus offline spatiotemporal image correlation (STIC) M-mode for the evaluation of cardiac longitudinal annular displacement in fetal growth restriction.

J Matern Fetal Neonatal Med 2018 Jul 31;31(14):1845-1850. Epub 2017 May 31.

a BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu) , Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona , Barcelona , Spain.

Purpose: Our first aim was to compare online M-mode with offline spatiotemporal image correlation (STIC) M-mode for assessing longitudinal annular displacement (LAD) in growth-restricted fetuses (FGR). Our second aim was to compare LAD measures of FGR cases with controls.

Materials And Methods: Prospective study including 40 FGR cases (defined estimated fetal weight and birth weight <10th centile) and 72 normally grown fetuses matched to cases by gestational age at scan. LAD was measured with online M-mode and offline STIC M-mode at the left and right ventricular free walls and septum in all fetuses.

Results: FGR cases had a significant decrease in LAD by STIC in all sites as compared to controls (e.g. right LAD in FGR mean 6.7 mm (SD 1.2) versus controls 7.2 mm (1.2), p = .033). There was a non-significant trend for lower values in FGR when using online M-mode (e.g. right LAD in FGR 6.9 mm (1.5) versus controls 7.4 mm (1.5), p = .084).

Conclusions: STIC M-mode seems a better method than online M-mode for detecting subtle changes in myocardial motion. STIC presents more precise results and allows an ideal placement of the M-mode arrow. These results confirm previous data suggesting decreased longitudinal motion in FGR.
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http://dx.doi.org/10.1080/14767058.2017.1330408DOI Listing
July 2018

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

Fetal Diagn Ther 2017 7;42(4):262-270. Epub 2017 Apr 7.

Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, 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.
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http://dx.doi.org/10.1159/000460247DOI Listing
July 2018

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

Fetal Diagn Ther 2017 26;41(3):191-196. Epub 2016 Jul 26.

BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1159/000448075DOI Listing
February 2018

Zidovudine treatment in HIV-infected pregnant women is associated with fetal cardiac remodelling.

AIDS 2016 06;30(9):1393-401

aBCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER) bDepartment of Cardiology, Thorax Clinic Institute, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona cInfectious Diseases Department, Hospital Clinic, Fundació Clínic per a la Recerca Biomèdica (FCRB), University of Barcelona dICREA, Universitat Pompeu Fabra, Barcelona, Spain.

Objective: To evaluate the cardiac structure and function of the fetuses of pregnant women with HIV infection on combined antiretroviral treatment (cART) and the HIV-related and nonrelated determinants of abnormal findings.

Design: A prospective cohort study including 42-noninfected fetuses from HIV pregnant women on cART and 84 fetuses from non-HIV-infected women.

Methods: Fetal echocardiography was performed at 26-32 weeks of pregnancy to assess cardiac structure and function. The impact of maternal and perinatal factors on fetal cardiac remodelling was evaluated by multivariate regression analysis.

Results: Fetuses from HIV pregnant women on cART presented larger hearts and pericardial effusion together with thicker myocardial septal walls (mean 3.56 mm (SD 0.88) vs non-HIV mean 2.75 mm (SD 0.77); P = 0.002) and smaller left ventricular cavities (10.81 mm (SD 2.28) vs 12.3 mm (SD 2.54); P = 0.033). Fetuses from HIV women also presented signs of systolic (mitral systolic annular peak velocity 5.85 cm/s (SD 0.77) vs non-HIV 6.25 cm/s (SD 0.97); P = 0.007) and diastolic (isovolumic relaxation time 52 ms (SD 8.91) vs non-HIV 45 ms (SD 7.98); P < 0.001) dysfunction. In the multivariate analysis, maternal treatment with zidovudine was the only factor significantly associated with fetal cardiac changes (P = 0.014).

Conclusion: Fetuses from HIV-infected mothers on cART have cardiac remodelling and dysfunction, which might explain the cardiovascular changes described in childhood. Fetal cardiac remodelling was essentially associated with maternal treatment with zidovudine which challenges its use during pregnancy.
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http://dx.doi.org/10.1097/QAD.0000000000001066DOI Listing
June 2016

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

Fetal Diagn Ther 2016 28;39(4):269-78. Epub 2015 Nov 28.

BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clx00ED;nic and Hospital Sant Joan de Dx00E9;u), IDIBAPS, University of Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1159/000439527DOI Listing
February 2017

Intertwin crown-rump length discordance in the prediction of fetal anomalies, fetal loss and adverse perinatal outcome.

J Matern Fetal Neonatal Med 2016 Sep 23;29(17):2883-8. Epub 2015 Nov 23.

a Department of Maternal-Fetal Medicine , Institute Gynecology, Obstetrics and Neonatology, Hospital Clinic Barcelona , Catalonia , Spain and.

Objective: To assess the risks of fetal anomalies, fetal loss and adverse perinatal outcome in a cohort of first-trimester intertwin crown-rump length (CRL) discordant twins, stratified by chorionicity and the degree of CRL discordance.

Method: Four-hundred-and-seventy-one twin pregnancies were scanned during an 8-year period at 11-14 weeks, and those with an intertwin CRL discordance ≥10% were compared with concordant twins. Outcomes were also compared between monochorionic and dichorionic twins and between moderate (10-16%) and severe (>16%) discordance.

Results: Four-hundred-and-five twin pregnancies, 65 discordant and 340 concordant, were follow-up. Discordant twin pregnancies were at significant higher risk of chromosomal (OR = 11.42; 95% CI: 2.78-46.94) and structural anomalies (OR = 5.91; 95% CI: 2.25-15.54), spontaneous fetal loss (OR = 4.23; 95% CI: 1.79-10.01), birthweight discordance (OR = 2.8; 95% CI: 1.48-5.65) and small-for-gestational age (OR = 3.48; 95% CI: 1.78-6.79). Similar differences (except for birthweight discordance) were observed among dichorionic twins. Among monochorionic, increased frequencies were only seen for structural anomalies, birthweight discordance and small newborns. Severe CRL discordance presented with higher rates of structural anomalies, stillbirth, birthweight discordance and small newborns.

Conclusion: Intertwin CRL discordance (≥10%) results in an increased risk of fetal anomalies and growth restriction that increases in severe CRL discordance (≥16%).
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http://dx.doi.org/10.3109/14767058.2015.1107901DOI Listing
September 2016

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

Fetal Diagn Ther 2016 8;39(3):186-91. Epub 2015 Sep 8.

Maternal-Fetal Unit, Hospital Clx00ED;nico de Chile, University of Chile, Santiago, Chile.

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.
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http://dx.doi.org/10.1159/000439023DOI Listing
January 2017

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

Prenat Diagn 2015 Dec 13;35(12):1197-201. Epub 2015 Sep 13.

BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.

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.
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http://dx.doi.org/10.1002/pd.4671DOI Listing
December 2015

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

Fetal Diagn Ther 2016 25;39(2):90-9. Epub 2015 Jun 25.

Fetal Cardiology Unit, BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clinic and Hospital Sant Joan de Dx00E9;u), IDIBAPS, University of Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1159/000433430DOI Listing
December 2016

Transcervical chorionic villus sampling: a practical guide.

J Matern Fetal Neonatal Med 2016 11;29(8):1244-51. Epub 2015 Jun 11.

a Prenatal Diagnosis Unit, Institute Clinic of Gynecology, Obstetrics and Neonatology (ICGON), Hospital Clinic, University of Barcelona , Barcelona , Catalonia , Spain.

First trimester screening for fetal aneuploidies has made the implementation of diagnostic techniques essential. Chorionic villus sampling (CVS) is the method of choice for obtaining chorionic villi for molecular and cytogenetic analysis in the first trimester. Two techniques have been developed, a transcervical and a transabdominal. The selection criteria have been based historically on factors, such as placental location, parity, maternal weight and preference of the operator. In our institution, we developed an elevated level of expertise in the field of transcervical approach, resulting in good quality of samples and comparable fetal loss rate to other approaches. Despite three decades of transcervical CVS performance, little consensus in terms of its technique and clinical guidelines exists. Considering the expertise and the volume of procedures performed at our center, we suggest a practical clinical guideline for transcervical CVS.
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http://dx.doi.org/10.3109/14767058.2015.1043261DOI Listing
October 2016

Role of ovarian reserve markers, antimüllerian hormone and antral follicle count, as aneuploidy markers in ongoing pregnancies and miscarriages.

Fertil Steril 2015 May 18;103(5):1221-7.e2. Epub 2015 Mar 18.

Department of Maternal-Fetal Medicine, Institute Gynecology, Obstetrics and Neonatology, Hospital Clínic Barcelona, Catalonia, Spain. Electronic address:

Objective: To assess the role of two ovarian reserve markers, antimüllerian hormone (AMH) and antral follicle count (AFC), as markers of the background risk for fetal trisomy.

Design: Prospective study.

Setting: Tertiary referral hospital.

Patient(s): Assessment was carried out either in ongoing pregnancies or miscarriages in our center.

Intervention(s): AFC was assessed transvaginally during a routine (11-13 weeks) or referral scan. AMH was determined either during the first-trimester maternal serum markers assessment or in cases referred for chorionic villi sampling after the invasive procedure.

Main Outcome Measure(s): AMH reference ranges were constructed according to maternal age, and AMH- and AFC-derived ovarian ages were compared among three different cytogenetic groups (normal karyotype, autosomal trisomies, and other chromosomal anomalies) in both ongoing pregnancies and miscarriages.

Result(s): In autosomal trisomies, the median AFC-derived ovarian age was 3-5 years above the median maternal age. No differences were observed between AMH-derived ovarian age and maternal age.

Conclusion(s): AFC-derived ovarian biologic age reflects a more precise background risk for fetal aneuploidy that is not observed for AMH-derived age.
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http://dx.doi.org/10.1016/j.fertnstert.2015.02.022DOI Listing
May 2015

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

J Ultrasound Med 2014 Jun;33(6):1079-84

Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital Pavilion for Women, Houston, Texas USA (J.E., W.L., M.B.); Department of Obstetrics and Gynecology, William Beaumont Hospital, Royal Oak, Michigan USA (J.E., W.L.); Centro AGB Ultrasonografía, Clínica Sanatorio Aleman, Concepción, Chile (F.V.); Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia, i Neonatologia, Hospital Clinic, University of Barcelona, Barcelona, Spain (J.M.M., M.B.); and Department of Obstetrics and Gynecology, University of Rome Tor Vergata, Rome, Italy (G.R.).

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.
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http://dx.doi.org/10.7863/ultra.33.6.1079DOI Listing
June 2014

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

Hum Reprod 2014 Jun 27;29(6):1337-43. Epub 2014 Mar 27.

Department of Maternal-Fetal Medicine, Institute Gynecology, Obstetrics and Neonatology, Hospital Clínic Barcelona, Barcelona, Catalonia, Spain.

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.
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http://dx.doi.org/10.1093/humrep/deu055DOI Listing
June 2014

Chromosomal anomaly spectrum in early pregnancy loss in relation to presence or absence of an embryonic pole.

Fertil Steril 2010 Dec 31;94(7):2564-8. Epub 2010 May 31.

Institute of Gynecology, Obstetrics, and Neonatology, Hospital Clinic, University of Barcelona Medical School, Barcelona, Spain.

Objective: To compare the cytogenetic findings in a series of missed miscarriages evaluated by chorionic villus sampling, in relation to embryonic pole presence (embryonic or anembryonic).

Design: Prospective cross-sectional study.

Setting: Tertiary referral hospital.

Patient(s): Women presenting with a missed miscarriage.

Intervention(s): Transcervical chorionic villus sampling and cytogenetic studies in the chorionic villi with use of the semidirect method.

Main Outcome Measures(s): Embryonic pole presence or absence assessed by transvaginal ultrasound examination. Type of chromosomal anomalies found in both subgroups.

Result(s): Although the chromosomal abnormality rate was similar for miscarriages with absent or present embryo (61% vs. 68% respectively), frequencies for viable autosomal trisomies (2.3% vs. 19%) and monosomy X (0% vs. 9.2%) were significantly lower when no embryonic pole was seen.

Conclusion(s): Viable autosomal trisomies and monosomies X appear not to be a common cause of miscarriage with an early fetal demise (anembryonic miscarriage).
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http://dx.doi.org/10.1016/j.fertnstert.2010.04.011DOI Listing
December 2010

The prognostic role of uterine artery Doppler investigation in patients with severe early-onset preeclampsia.

Am J Obstet Gynecol 2010 Jun 29;202(6):559.e1-4. Epub 2010 Mar 29.

Department of Maternal-Fetal Medicine, ICGON, Fetal and Perinatal Medicine Research Group (IDIBAPS), and Center of Biomedical Research on Rare Diseases (CIBER-ER), Hospital Clinic-University of Barcelona, Spain.

Objective: The purpose of this study was to evaluate the prediction capacity of uterine artery Doppler investigation for maternal and neonatal complications in women who are admitted with severe early-onset preeclampsia.

Study Design: A uterine artery Doppler examination was performed at admission for patients with severe early-onset (<34 weeks of gestation) preeclampsia. The maternal and neonatal outcome of women with abnormal uterine Doppler results was compared with those with normal Doppler results.

Results: One hundred twenty patients were included. In 53% of them, uterine Doppler results were abnormal. This group had a lower gestational age at delivery (30.2 vs 32.7 weeks; P < .001) and a higher proportion of small-for-gestational age infants (87.5% vs 67.9%; P = .009). Neonatal (40.6% vs 14.3%; P = .01) and maternal (28.1% vs 5.4%; P = .001) complications were more common in the abnormal uterine Doppler group.

Conclusion: Women with severe early-onset preeclampsia are at higher risk of maternal and neonatal complications if abnormal uterine blood flow is present.
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http://dx.doi.org/10.1016/j.ajog.2010.01.048DOI Listing
June 2010

Acute coronary artery vasospasm associated with misoprostol for termination of pregnancy.

Fetal Diagn Ther 2010 11;27(3):174-7. Epub 2010 Mar 11.

Department of Maternal-Fetal Medicine, Institut Clínic de Ginecologia, Obstetrícia i Neonatologia (ICGON), Hospital Clinic, University of Barcelona, Barcelona, Spain.

Prostaglandin E(1) analogues, gemeprost and misoprostol, are the most widely used drugs for medical termination of pregnancy within the first two trimesters of pregnancy. Gemeprost has been reported to be associated with acute cardiovascular accidents in a few cases, but no adverse cardiovascular events have been reported with misoprostol. For this reason, misoprostol has been considered a potentially safer drug and is widely recommended as a first-choice drug in combination with mifepristone. We report a case of a 32-year-old woman with active smoking and obesity, who developed an episode of transient acute coronary artery vasospasm following the administration of intravaginal misoprostol. This report illustrates that misoprostol can also be associated with acute coronary events, although it remains to be evaluated whether the risk is similar or lower to gemeprost.
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http://dx.doi.org/10.1159/000295923DOI Listing
July 2010

Gestational age-specific cutoff levels of TDx-FLM II for the prediction of neonatal respiratory distress syndrome.

Fetal Diagn Ther 2009 29;25(4):392-6. Epub 2009 Sep 29.

Department of Maternal-Fetal Medicine, Hospital Clínic, Institut d'Investigacions Biomèdiques Augusto Pi i Sunyer, University of Barcelona, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.

Aim: To construct a predictive model for respiratory distress syndrome (RDS) from gestational age (GA) at delivery and TDx-FLM II value.

Methods: Pregnant women who underwent an amniocentesis in which TDx-FLM II was determined were included in the study. A model for the occurrence of RDS was constructed by means of a logistic regression procedure from TDx-FLM II values and GA at delivery.

Results: The mean value of TDx-FLM II was 47.11 mg/g. The mean GA at delivery was 33.4 weeks. The incidence of RDS was 7.8% (18/231). The optimal cutoff of predicted risk for respiratory distress was found to be 8.8%, resulting in a sensitivity and specificity of 89 and 83%, respectively.

Conclusions: The adjustment of the TDx-FLM II value for GA at delivery results in a significant improvement in the predictive capacity of the test for the occurrence of RDS. The use of GA-specific cutoff values may simplify clinical decisions.
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http://dx.doi.org/10.1159/000236152DOI Listing
December 2009

Efficacy of two regimens of misoprostol for early second-trimester pregnancy termination.

Fetal Diagn Ther 2005 Nov-Dec;20(6):544-8

Obstetrics and Gynecology, Institut Clínic de Ginecologia, Obstetrícia i Neonatologia, Hospital Clínic de Barcelona, Barcelona, Spain.

Objective: To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination.

Methods: This is a prospective study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks. Two regimens of misoprostol were used. Group 1: 400 microg of oral plus 400 microg vaginal misoprostol every 8 h (combined regimen) and group 2: 400 microg of vaginal misoprostol every 3 h up to a maximum of five doses (vaginal regimen).

Results: The induction-to-abortion interval was significantly longer in group 1 (25.5 +/- 24.45 h) than in group 2 (15 +/- 7.14 h) (p = 0.016). The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7% in group 2 (p = 0.006). The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders.

Conclusions: Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination.
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http://dx.doi.org/10.1159/000088048DOI Listing
January 2006
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