E. Gratacós

University of Barcelona, Barcino, Catalonia, Spain

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Publications (671)2368.05 Total impact


  • No preview · Article · Feb 2016 · Journal of Maternal-Fetal and Neonatal Medicine

  • No preview · Article · Feb 2016
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    ABSTRACT: The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of BOLD signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment.
    No preview · Article · Jan 2016 · Cortex
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    ABSTRACT: The pathogenic basis of abnormal placentation and dysfunction in preeclampsia (PE) is highly complex and incompletely understood. Secretory sphyngomyelinase activity (S-ASM) was analyzed in plasma samples from 158 pregnant women developing PE and 112 healthy pregnant controls. Serum PlGF, sFlt-1, s-Endoglin and sVCAM were measured. Results showed S-ASM activity to be higher in women who later developed PE than in those with uncomplicated pregnancies (40.6% and 28.8% higher in the late- and early-onset groups, respectively). Plasma S-ASM activity correlated significantly with circulating markers of endothelial damage in the late-PE group (endoglin and sVCAM-1), with plasma cholesterol and total lipid levels. However, these significant associations were not observed in the early- PE or control groups. This work provides the first evidence of significantly elevated circulating S-ASM activity in the first trimester of pregnancy in women who go on to develop PE; thus, it may be deduced that the circulating form of ASM is biologically active in PE and could contribute to promoting endothelial dysfunction and cardiovascular programming. Plasma S-ASM measurement may have clinical relevance as a further potential biomarker contributing to the earliest identification of women at risk of developing preeclampsia.
    No preview · Article · Jan 2016 · Biological Chemistry
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    ABSTRACT: Background: Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described using different magnetic resonance based methodologies, including changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. Objectives: In this study we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as imaging biomarker of altered neurodevelopment. Methods: We included a group of 24 intrauterine growth restriction and 27 controls that were scanned at one year of age acquiring T1-weighted and 30 directions diffusion MR images. Each subject brain was segmented in 93 regions using Anatomical Automatic Labeling atlas and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomical criteria. Within the streamlines resulting from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics including number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socio-emotional, cognitive, and motor scales from Bayley Scale at two years of age. Results: Reduced fractional anisotropy (cortico-striatal-thalamic 0.319 (0.018) vs 0.315 (0.015), p= 0.010; motor 0.322 (0.019) vs 0.319 (0.020), p=0.019) and integrity cortico-striatal-thalamic 0.407 (0.040) vs 0.399 (0.034), p= 0.018; motor 0.417 (0.044) vs 0.409 (0.046), p=0.016) in both networks were observed in intrauterine growth restriction group with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in IUGR children. Motor network metrics were specifically correlated with motor scale results (fractional anisotropy rho= 0.857, integrity rho= 0.740) and cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy rho= 0.793, integrity rho= 0.762) and socio-emotional scale (fractional anisotropy rho= 0.850, integrity rho= 0.877) CONCLUSIONS: These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in IUGR shows the potential to use this approach in order to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants at risk due to intrauterine growth restriction and other prenatal diseases.
    No preview · Article · Dec 2015 · American journal of obstetrics and gynecology

  • No preview · Article · Nov 2015 · Zeitschrift für Geburtshilfe und Neonatologie
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    ABSTRACT: We report the successful use of fetoscopy to treat a case of prolapsed ureterocele in a female fetus. A diagnosis of a double renal system with an intravesical ureterocele was performed at 21 weeks' gestation. Follow-up exams showed that the ureterocele was obstructing the bladder outlet causing severe megacystis, bilateral hydronephrosis and progressive oligohydramnios. Those findings suggested a poor prognosis and therefore the patient was referred to our Fetal Therapy Unit to consider prenatal treatment. The ultrasound evaluation at admission confirmed severe bilateral hydronephrosis with pelvic and caliceal dilatation, but, surprisingly, the amniotic fluid was normal and no image of ureterocele could be identified into the bladder. Instead, a cystic image between the external genitalia could be observed, leading us to the diagnosis of a prolapsed ureterocele causing intermittently severe obstruction of the urethra. Due to the unpredictable course of the malformation, parents were counselled about the uncertain fetal prognosis and therefore fetal surgery to decompress the urinary system was proposed, with the agreement of the paediatric urologist. After extensive discussion and counselling, a fetoscopic operation was designed and indicated. The procedure consisted in opening the cystic mass by means of firing with contact diode laser until the opening of the ureterocele was achieved. After the surgery, resolution of the megacystis, with reduction of the hydronephrosis, and persistent normalization of the amniotic fluid volume were observed. The pregnancy continued uneventfully and a normal female infant was born at term at her local hospital. The child is developing normally with normal renal function at 4 years old. Our report demonstrates that fetoscopic decompression of a distal urethra obstruction is feasible in the rare event of congenital prolapsed ureterocele. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Ultrasound in Obstetrics and Gynecology
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    Full-text · Article · Nov 2015 · Journal of Developmental Origins of Health and Disease
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    ABSTRACT: Introduction: Recent studies have reported variations of up to 30% between different ultrasound machines for tissue Doppler imaging (TDI), a problem that can significantly impact clinical diagnosis, patient management and research studies. The objective of this study was to assess repeatability and agreement between fetal myocardial peak velocities evaluated by TDI with two different ultrasound systems. Materials and methods: Systolic (S'), early (E') and late (A') diastolic myocardial peak velocities at mitral and tricuspid annuli as well as at the basal septum were evaluated by spectral TDI in 150 fetuses using two different ultrasound systems: Siemens Antares (Siemens Medical Systems, Malvern, Pa., USA) and Vivid Q (General Electric Healthcare, Horten, Norway). A method comparison study was performed, calculating intraclass correlation coefficients (ICC), and agreement was assessed by Bland-Altman plots. Results: Annular peak velocities showed lower values when measured by Vivid Q compared to values measured by Siemens Antares. ICC ranged from 0.07 (septal S') to 0.33 (right A'), showing very poor repeatability for clinical application. Agreement between the two systems was also poor, with high coefficients of variation for all measurements. Conclusions: Fetal annular peak velocities obtained with different ultrasound systems are not directly comparable. This is consistent with previous data in adults and warrants the need of system-specific reference values, suggesting that the same ultrasound machine should be used for longitudinal follow-up.
    Full-text · Article · Oct 2015 · Fetal Diagnosis and Therapy
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    ABSTRACT: OBJECTIVE: To evaluate in normally growing fetuses at routine 32-36 weeks scan the performance of maternal angiogenic factors, Doppler and ultrasound indices in predicting smallness for gestational age (SGA) at birth. METHODS: A cohort of 1,000 singleton pregnancies with normal estimated fetal weight (EFW, ≥10th centile) at 32-36 weeks scan was included. At inclusion, Doppler indices (mean uterine artery pulsatility index [mUtA-PI], cerebroplacental ratio and normalized umbilical vein blood flow by EFW (ml/min/kg) were evaluated, and blood samples were collected and frozen. Nested in this cohort, maternal circulating placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by enzyme-linked immunosorbent assay in all cases with a birth weight <10th centile by customized standards and in an equivalent number of controls (birth weight ≥10th centile). RESULTS: 160 cases were included (80 SGA and 80 controls). EFW (2,128 vs. 2,279 g, p < 0.001), mUtA-PI z-values (-0.25 vs. -0.65, p = 0.034) and sFlt-1/PlGF ratio (11.10 vs. 6.74, p < 0.005) were lower in SGA. The combination of sFlt-1/PlGF ratio and EFW resulted in a 66.3% detection rate for subsequent SGA, with 20% of false-positives. Fetal Doppler indices were not predictive of SGA. CONCLUSIONS: In normally growing fetuses, maternal angiogenic factors add to ultrasound parameters in predicting subsequent SGA at birth. This supports further research to investigate composite scores in order to improve the definition and identification of fetal growth restriction.
    Full-text · Article · Oct 2015 · Fetal Diagnosis and Therapy
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    ABSTRACT: Background: Our aim was to determine the influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction (FGR). Methods: A cohort study including 81 children with birthweight <10 centile (FGR) and 121 with adequate fetal growth (AGA). Cardiovascular end-points were left ventricular sphericity index (LVSI), carotid intima-media thickness (cIMT) and blood pressure (BP) at 4-5 years of age. The combined effect of FGR and postnatal variables -including breastfeeding, fat dietary intake and body-mass index (BMI)- on cardiovascular end-points was assessed by linear and robust regressions. Results: FGR was the strongest predictor of cardiovascular remodeling in childhood, leading to lower LVSI and increased cIMT and BP as compared to AGA. Breastfeeding>6 months (coefficient 0.0982) and healthy-fat dietary intake (coefficient -0.0128) showed an independent beneficial effect on LVSI and cIMT respectively. Overweight/obesity induced an additional increment of 1SD on cIMT in FGR children (interaction coefficient 0.0307) when compared with its effect in AGA. BMI increased systolic BP (coefficient 0.7830) while weight catch-up increased diastolic BP (coefficient 4.8929). Conclusions: Postnatal nutrition ameliorates cardiovascular remodeling induced by FGR. Breastfeeding and healthy-fat dietary intake improved while increased BMI worsened cardiovascular end-points, which opens opportunities for targeted postnatal interventions from early life.Pediatric Research (2015); doi:10.1038/pr.2015.182.
    Full-text · Article · Sep 2015 · Pediatric Research
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    ABSTRACT: Background: This study was performed to assess the role of lipopolysaccharide modulators as a marker of microbial translocation among human immunodeficiency virus (HIV)-infected women during pregnancy and to evaluate their association with preterm delivery. Methods: The study had a prospective cohort design and was performed at the Hospital Clínic in Barcelona, Spain. Thirty-six pregnant women with and 36 without HIV infection, matched on the basis of age and parity, were included. Maternal blood samples were obtained during the first trimester, during the third trimester, and at delivery. Levels of soluble CD14 (sCD14), human lipopolysaccharide-binding protein (LBP), immunoglobulin M endotoxin core antibodies to lipopolysaccharide (EndoCAb), and interleukin 6 (IL-6) were determined. Fetal cord blood levels of sCD14, LBP, and IL-6 were determined. Results were compared between groups. Results: First trimester sCD14 and LBP levels and third trimester sCD14 levels were significantly higher in the HIV-infected group. HIV-infected women with preterm births and spontaneous preterm births had significantly increased levels of sCD14 throughout pregnancy and significantly increased levels of LBP during the first trimester, compared with HIV-infected women with delivery at term or with HIV-negative women. On multivariate analysis, an independent association was observed between first trimester sCD14 levels and preterm delivery among HIV-infected women. Conclusions: This is the first study to assess inflammatory markers related to microbial translocation during pregnancy among HIV-infected women. Higher levels of sCD14 and LBP were observed in HIV-infected pregnant women and were associated with preterm delivery.
    No preview · Article · Sep 2015 · The Journal of Infectious Diseases
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    ABSTRACT: OBJECTIVE: To evaluate use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingency basis in an unselected population, according to the risk accrued at second trimester. METHODS: Maternal characteristics, fetal biometry and uterine Doppler at second trimester were subjected to logistic regression to estimate late FGR risk (birthweight <3rd percentile; or between 3rd and 10th percentiles, plus abnormal Doppler). Based on above second-trimester estimates, strategies for performing contingent third-trimester scans in 10%, 25%, or 50% of the cohort were tested against a strategy of routine scan at 32+0-33+6 weeks. RESULTS: The models were constructed on 1393 and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At second trimester, a posteriori first-trimester risk (baseline a priori risk and blood pressure) combined with abdominal circumference and uterine Doppler (a posteriori second-trimester risk) yielded an AUC of 0.81 (95% CI 0.74-0.87) (detection rate (DR) of 43.1% at 10% false positive rate (FPR)). Finally, the combination of a posteriori second-trimester risk plus third-trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI 0.88-0.96) (DR of 74% at 10% FPR). By variably subjecting 10%, 25%, or 50% of the study population to third-trimester scans, based on a posteriori second-trimester risk, AUC were 0.81 (0.75-0.88), 0.84 (0.78-0.91) and 0.89 (0.84-0.94), respectively. Only the 50% contingency model proved statistically equivalent to routinely performing third-trimester scans (AUC 0.92 (95% CI 0.88-0.96)]; p=0.11). CONCLUSION: A strategy of selecting 50% of a study population for third-trimester scans, based on accrued risk at second trimester, proved equivalent to routine third-trimester scanning in predicting late FGR.
    Full-text · Article · Sep 2015 · Ultrasound in Obstetrics and Gynecology
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    ABSTRACT: 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.
    No preview · Article · Sep 2015 · Fetal Diagnosis and Therapy

  • No preview · Article · Sep 2015 · Ultrasound in Obstetrics and Gynecology
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    Full-text · Article · Sep 2015 · Ultrasound in Obstetrics and Gynecology

  • No preview · Article · Sep 2015 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
  • V. Borobio · M. Grande · M. Bennasar · A. Borrell · E. Gratacós

    No preview · Article · Sep 2015 · Ultrasound in Obstetrics and Gynecology

  • No preview · Article · Sep 2015 · Ultrasound in Obstetrics and Gynecology
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    ABSTRACT: Objectives Intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is poorly documented. We evaluated longitudinally the association between cardiovascular remodelling in fetal life and at 6 months of age in IUGR.MethodsA cohort of 80 IUGR (estimated fetal and birth weight<10th centile, delivery >34 weeks’ gestation) was compared with 80 normally grown control fetuses, and followed at 6 months of corrected age. Cardiovascular evaluation included a comprehensive echocardiographic assessment (fetuses and infants), and blood pressure and aortic intima-media thickness (aIMT) in infants. Parameters were adjusted by gender, gestational age at delivery, prenatal glucocorticoid exposure, cesarean section, neonatal intensive care and body surface area by linear regression analysis.ResultsWhen compared to controls, IUGR showed more globular cardiac shape both pre- and postnatally (infant left sphericity index: control 1.92 vs. IUGR 1.67, p-<0.001), as well as signs of systolic longitudinal dysfunction (infant mitral lateral annular S’ peak velocity: control 7.9 vs. IUGR 6.4 cm/s, p-<0.001; tricuspid annular plane systolic excursion: control 16.0 vs. IUGR 14.2 mm, p-<0.001) and diastolic dysfunction (isovolumetric relaxation time: control 50 vs. IUGR 57 ms, p-<0.001). In addition, IUGR infants had increased mean blood pressure (mean: control 61 vs. IUGR 70 mmHg, p-<0.001) and maximum aIMT (control 0.57 vs. IUGR 0.66 mm, p-<0.001).Conclusions Primary cardiovascular changes in IUGR are already present in utero and persist at 6 months of age. The data supports prenatal cardiovascular remodelling as a mechanistic pathway of increased risk in IUGR.
    No preview · Article · Sep 2015 · Ultrasound in Obstetrics and Gynecology

Publication Stats

7k Citations
2,368.05 Total Impact Points

Institutions

  • 1993-2016
    • University of Barcelona
      • • Department of Obstetrics and Gynecology, Pediatrics, Radiology and Anatomy
      • • Department of Medicine
      Barcino, Catalonia, Spain
  • 2015
    • Hospital Clínico Universidad de Chile
      CiudadSantiago, Santiago Metropolitan, Chile
  • 2014-2015
    • Hospital Sant Joan de Déu
      Barcino, Catalonia, Spain
  • 1994-2015
    • Hospital Clínic de Barcelona
      • Servicio de Medicina Materno Fetal
      Barcino, Catalonia, Spain
  • 2013-2014
    • Fetal Medicine Barcelona
      Barcino, Catalonia, Spain
  • 2011-2014
    • Centro de Investigación Biomédica en Red de Enfermedades Raras
      Valenza, Valencia, Spain
  • 2008-2014
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2008-2012
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
  • 2008-2010
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 2009
    • Royal Prince Alfred Hospital
      Camperdown, New South Wales, Australia
  • 2003-2009
    • Universitair Ziekenhuis Leuven
      • Department of Gynaecology and obstetrics
      Louvain, Flanders, Belgium
  • 2001-2009
    • University Hospital Vall d'Hebron
      • Department of Obstetrics
      Barcino, Catalonia, Spain
    • ՊԵՐԻՆԱՏՈԼՈԳԻԱՅԻ, ՄԱՆԿԱԲԱՐՁՈՒԹՅԱՆ ԵՎ ԳԻՆԵԿՈԼՈԳԻԱՅԻ ԻՆՍՏԻՏՈՒՏ
      Ayrivan, Yerevan, Armenia
  • 2002-2008
    • Autonomous University of Barcelona
      • Department of Biochemistry and Molecular Biology
      Cerdanyola del Vallès, Catalonia, Spain
  • 2006-2007
    • Southern Medical Clinic
      San Fernando, City of San Fernando, Trinidad and Tobago
  • 2004
    • University of Rochester
      Rochester, New York, United States
  • 1999-2002
    • University of Leuven
      • Faculty of Medicine
      Louvain, Flanders, Belgium