F. Figueras

Centro de Investigación Biomédica en Red de Enfermedades Raras, Valenza, Valencia, Spain

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Publications (427)1074.85 Total impact

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    ABSTRACT: Objective To develop the best first trimester screening model for preeclampsia (PE) based on maternal characteristics, biophysical parameters, and angiogenic factors in a low-risk population.MethodsA prospective cohort of 9,462 pregnancies undergoing first-trimester screening. Logistic regression predictive models were developed for early and late PE (cut-off 34 weeks’ gestation at delivery). Data included the a priori risk (maternal characteristics), mean arterial pressure (MAP) and uterine artery (UtA) Doppler (11–13 weeks) in all cases. Plasma levels (8–11 weeks) of hCG, PAPP-A, placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFtl-1) was analyzed using a nested case-control study design.ResultsThe best model for early PE (n = 57, 0.6%) included a priori risk, MAP, UtA Doppler, PlGF and sFlt-1 achieving detection rates (DR) of 87.7% and 91.2% for 5% and 10% false-positive rates (FPR), respectively (AUC: 0.98 [95%CI: 0.97-0.99]). For late PE (n = 246, 2.6%), the best model included the a priori risk, MAP, UtA Doppler, PlGF and sFlt-1 achieving DR of 68.3% and 76.4% at 5% and 10% of FPR, respectively (AUC: 0.87 [95%CI: 0.84-0.90]).ConclusionPE can be predicted with high accuracy in general obstetric populations with a low-risk for PE, by combined algorithms. Angiogenic factors substantially improved the prediction. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 10/2014; · 2.68 Impact Factor
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    ABSTRACT: In utero exposure of fetuses to tobacco is associated with reduced birth weight. We hypothesized that this may be due to the toxic effect of carbon monoxide (CO) from tobacco, which has previously been described to damage mitochondria in non-pregnant adult smokers. Maternal peripheral blood mononuclear cells (PBMCs), newborn cord blood mononuclear cells (CBMCs) and placenta were collected from 30 smoking pregnant women and their newborns and classified as moderate and severe smoking groups, and compared to a cohort of 21 non-smoking controls. A biomarker for tobacco consumption (cotinine) was assessed by ELISA (enzyme-linked immunosorbent assay). The following parameters were measured in all tissues: mitochondrial chain complex IV [cytochrome c oxidase (COX)] activity by spectrophotometry, mitochondrial DNA levels by reverse transcription polymerase chain reaction, oxidative stress by spectrophotometric lipid peroxide quantification, mitochondrial mass through citrate synthase spectrophotometric activity and apoptosis by Western blot parallelly confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assay in placenta. Newborns from smoking pregnant women presented reduced birth weight by 10.75 percent. Materno-fetal mitochondrial and apoptotic PBMC and CBMC parameters showed altered and correlated values regarding COX activity, mitochondrial DNA, oxidative stress and apoptosis. Placenta partially compensated this dysfunction by increasing mitochondrial number; even so ratios of oxidative stress and apoptosis were increased. A CO-induced mitotoxic and apoptotic fingerprint is present in smoking pregnant women and their newborn, with a lack of filtering effect from the placenta. Tobacco consumption correlated with a reduction in birth weight and mitochondrial and apoptotic impairment, suggesting that both could be the cause of the reduced birth weight in smoking pregnant women.
    Addiction Biology 10/2014; · 5.91 Impact Factor
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    ABSTRACT: Objective The objective of this study was to develop an integrated model with the best performing criteria to predict adverse outcome in small-for-gestational age (SGA) pregnancies.Methods Cohort of 509 pregnancies with suspected SGA fetus eligible for trial of labor was recruited prospectively, and data on the perinatal outcome recorded. A predictive model for the occurrence of emergency cesarean delivery for non-reassuring fetal status or neonatal acidosis was constructed using the Decision Tree Analysis algorithm (SPSS 19.0), with predictors: maternal age, body mass index, smoking, nulliparity, gestational age at delivery, labor onset (induced vs. spontaneous), estimated fetal weight (EFW), umbilical artery pulsatility index (PI), mean uterine artery (UtA) PI, middle cerebral artery PI, and cerebroplacental ratio (CPR).ResultsAn adverse outcome occurred in 134 (26.3%) cases. The best performing combination to define high risk SGA was the presence of CPR < 10th centile, a mean UtA PI > 95th centile or an EFW < 3rd centile. The algorithm showed a sensitivity, specificity, positive and negative predicted value for adverse outcome of 82.8% (95% CI 75.1%-88.6%), 47.7% (95% CI 42.6%-52.9%), 36.2% (95% CI 30.8%-41.8%) and 88.6% (95% CI 83.2%-92.5%), respectively. Positive and negative likelihood ratios were 1.58 and 0.36.Conclusions Our model could be used as a diagnostic tool to discriminate SGA pregnancies at risk of adverse perinatal outcome.
    Ultrasound in Obstetrics and Gynecology 10/2014; · 3.56 Impact Factor
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    ABSTRACT: Objective To evaluate the clinical value of uterine artery Doppler in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses.Study DesignUterine artery (UtA) Doppler, cerebroplacental ratio (CPR), and middle cerebral artery (MCA) pulsatility indices (PI) were weekly evaluated from diagnosis until 24 hrs before labor induction in a cohort of 327 SGA fetuses with normal umbilical artery PI (<95th centile) delivered above 37 weeks. Differences in the sequence of changes of CPR and MCA PI <5th centile between the group with normal and abnormal uterine artery Doppler at diagnosis were analyzed by survival analysis. In addition, the value of uterine artery Doppler, alone or in combination with brain Doppler before delivery, to predict cesarean delivery (CD), CD for nonreassuring fetal status (NRFS), neonatal acidosis (NA) and neonatal hospitalization was evaluated by logistic regression adjusted by gestational age at birth and birthweight percentile.ResultsAbnormal uterine artery at diagnosis was associated with a higher risk of developing abnormal brain Doppler before labor induction (62.7% vs. 34.6%, p < 0.01). Abnormal UtA Doppler was associated with a higher risk of intrapartum CD (52.2% vs. 37.3% with normal UtA Doppler, p = 0.03), CD for NRFS (35.8% vs. 23.1%, p = 0.03), NA (10.4% vs. 7.7%, p = 0.47) and neonatal hospitalization (23.9% vs. 16.5%, respectively, p = 0.16). Logistic regression analysis indicated that UtA Doppler had not significant association with adverse perinatal outcome independently of brain Doppler.Conclusion Uterine artery Doppler predicts adverse outcome, but it does not help to improve the predictive value of brain Doppler. However, at the time of diagnosis it identifies the subgroup of fetuses at highest risk of progression to abnormal brain Doppler.
    Ultrasound in Obstetrics and Gynecology 10/2014; · 3.56 Impact Factor
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    ABSTRACT: We derive the vertical velocities of disk stars in the range of Galactocentric radii of R=5-16 kpc within 2 kpc in height from the Galactic plane. This kinematic information is connected to dynamical aspects in the formation and evolution of the Milky Way, such as the passage of satellites and vertical resonance and determines whether the warp is a long-lived or a transient feature. We used the proper motions of the PPMXL survey, correcting of systematic errors with the reference of quasars. From the color-magnitude diagram K versus (J-K) we selected the standard candles corresponding to red clump giants and used the information of their proper motions to build a map of the vertical motions of our Galaxy. We derived the kinematics of the warp both analytically and through a particle simulation to fit these data. Complementarily, we also carried out the same analysis with red clump giants spectroscopically selected with APOGEE data, and we predict the improvements in accuracy that will be reached with future Gaia data. A simple model of warp with the height of the disk z_w(R,phi)=gamma (R-R_sun) sin(phi-phi_w) fits the vertical motions if d(gamma)/dt/gamma=-34+/-17 Gyr^{-1}; the contribution to d(gamma)/dt comes from the southern warp and is negligible in the north. The vertical motion in the warp apparently indicates that the main S-shaped structure of the warp is a long-lived feature, whereas the perturbation that produces an irregularity in the southern part is most likely a transient phenomenon. With the use of the Gaia end-of-mission products together with spectroscopically classified red clump giants, the precision in vertical motions can be increased by an order of magnitude at least.
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    ABSTRACT: The purpose of the study was to evaluate the association between a quantitative texture analysis of early neonatal brain ultrasound images and later neurobehavior in preterm infants. A prospective cohort study including 120 preterm (<33 wk of gestational age) infants was performed. Cranial ultrasound images taken early after birth were analyzed in six regions of interest using software based on texture analysis. The resulting texture scores were correlated with the Neonatal Behavioural Assessment Scale (NBAS) at term-equivalent age. The ability of texture scores, in combination with clinical data and standard ultrasound findings, to predict the NBAS results was evaluated. Texture scores were significantly associated with all but one NBAS domain and better predicted NBAS results than clinical data and standard ultrasound findings. The best predictive value was obtained by combining texture scores with clinical information and ultrasound standard findings (area under the curve = 0.94). We conclude that texture analysis of neonatal cranial ultrasound-extracted quantitative features that correlate with later neurobehavior has a higher predictive value than the combination of clinical data with abnormalities in conventional cranial ultrasound.
    Ultrasound in Medicine & Biology 09/2014; · 2.46 Impact Factor
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    ABSTRACT: The purpose of this investigation was to study the risk of intrauterine growth restriction in human immunodeficiency virus (HIV)-infected women and to describe the associated risk factors. A cohort study was performed among HIV-infected women who delivered in a single tertiary centre in Barcelona, Spain, from January 2006 to December 2011. Consecutive singleton pregnancies delivered beyond 22 weeks of pregnancy were included. Intrauterine growth restriction (IUGR) was defined as a birth weight below the 10th customised centile for gestational age and IUGR babies were compared to non-IUGR newborns. Intrauterine Doppler findings were described among IUGR foetuses. Baseline characteristics, HIV infection data and perinatal outcome were compared between groups. The results were adjusted for potential confounders. A total of 156 singleton pregnancies were included. IUGR occurred in 23.4 % of cases (38/156). In two-thirds of the cases detected before birth, Doppler abnormalities compatible with placental insufficiency were observed. IUGR pregnancies presented a worse perinatal outcome, mainly due to a higher risk of iatrogenic preterm delivery [adjusted odds ratio 6.9, 95 % confidence interval (CI) 1.4-33.5]. IUGR foetuses also had a higher risk of emergent Caesarean section and neonatal intensive care unit admission. No cases of intrauterine foetal death occurred. A high rate of IUGR was observed among HIV pregnancies, and it was associated with adverse perinatal outcomes, mainly iatrogenic preterm and very preterm birth due to placental insufficiency. Our results support that ultrasound detection and follow-up of IUGR foetuses should be part of routine antenatal care in this high-risk population to improve antenatal management.
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    ABSTRACT: Objectives: We used magnetic resonance spectroscopy (MRS) to evaluate brain metabolic differences in small fetuses near term as compared to appropriate for gestational age (AGA) fetuses. Study Design: 71 term small fetuses (estimated fetal weight <10th centile for gestational age with normal umbilical artery Doppler sonography) were subclassified as late intrauterine growth restriction (IUGR) (n = 50) or small for gestational age (SGA) (n = 21), and compared with 65 AGA fetuses. IUGR was defined by either abnormal middle cerebral artery, abnormal uterine artery Doppler sonography or estimated fetal weight <3rd centile. All participants underwent brain magnetic resonance imaging at 37 weeks of gestation, and single-voxel magnetic resonance spectra were obtained from the frontal lobe on a 3-tesla scanner. N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr) and Cho/Cr ratios were calculated and compared between cases and controls. The association of the metabolic ratios with the study groups was tested. Results: After MRS processing and applying quality control criteria, 31 spectra from late-onset IUGR, 11 from SGA and 30 from AGA fetuses were selected for further analysis. Both SGA and late-onset IUGR fetuses showed significantly reduced NAA/Cho levels when compared to AGA fetuses. This decrease followed a linear trend across the three clinical groups that were considered. Conclusions: Both SGA and late-onset IUGR fetuses showed differences in MRS brain metabolic ratios. The findings suggest that despite near-normal perinatal outcomes, SGA fetuses are not constitutionally small and may represent a form of growth disorder that needs to be clarified. © 2014 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 08/2014; · 1.90 Impact Factor
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    ABSTRACT: Objective To examine whether a first-trimester strategy of secondary prevention for preeclampsia increases anxiety in pregnant women.Methods The anxiety levels of a cohort of women screened for preeclampsia at first trimester were measured by the Spielberg State Anxiety Inventory [STAI-S] and compared between women screened as low and high risk. In a subgroup of women the anxiety levels were additionally measured at second and third trimester. A General Linear Model (GLM) model for repeated measurements was performed to adjust for potential confounders (age, nulliparity and socio-economic level).ResultsA total of 255 women (135 low-risk and 120 high-risk) were evaluated. No differences were found in the mean STAI-S scores between low and high risk women: 35 (SD 9.9) and 34.6 (SD 10.1) (p = 0.77). The proportion of women with high anxiety was not significantly different between groups (28/134[20.7%]vs.24/120 [20%]; p = 0.88). No differences were found in the subgroups (51 low-risk and 50 high-risk) in which the anxiety levels were also measured at second and third trimester: 35.8 (SD 8.8)vs.35.2 (SD9.7) [p = 0.74] and 37.2 (SD 9.4)vs.35.3 (SD 8.6) [p = 0.3]. These differences remained non-significant after adjustment for potential confounders.ConclusionA strategy of first-trimester screening for preeclampsia does not increase maternal anxiety. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 08/2014; · 2.68 Impact Factor
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    ABSTRACT: Pregnancy-induced hypertensive disorders can lead to maternal and perinatal morbidity and mortality, but the cause of these conditions is not well understood. We have systematically reviewed and performed a meta-analysis of epidemiological studies investigating the association between exposure to ambient air pollution and pregnancy-induced hypertensive disorders including gestational hypertension and preeclampsia. We searched electronic databases for English language studies reporting associations between ambient air pollution and pregnancy-induced hypertensive disorders published between December 2009 and December 2013. Combined risk estimates were calculated using random-effect models for each exposure that had been examined in ≥4 studies. Heterogeneity and publication bias were evaluated. A total of 17 articles evaluating the impact of nitrogen oxides (NO2, NOX), particulate matter (PM10, PM2.5), carbon monoxide (CO), ozone (O3), proximity to major roads, and traffic density met our inclusion criteria. Most studies reported that air pollution increased risk for pregnancy-induced hypertensive disorders. There was significant heterogeneity in meta-analysis, which included 16 studies reporting on gestational hypertension and preeclampsia as separate or combined outcomes; there was less heterogeneity in findings of the 10 studies reporting solely on preeclampsia. Meta-analyses showed increased risks of hypertensive disorders in pregnancy for all pollutants except CO. Random-effect meta-analysis combined odds ratio associated with a 5-µg/m(3) increase in PM2.5 was 1.47 (95% confidence interval, 1.27-1.68) for combined pregnancy-induced hypertensive disorders and 1.30 (95% confidence interval, 1.11-1.48) for preeclampsia. Our results suggest that exposure to air pollution increases the risk of pregnancy-induced hypertensive disorders.
    Hypertension 06/2014; · 6.87 Impact Factor
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    ABSTRACT: Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used as biomarkers to monitor brain changes produced by experimental therapies in IUGR animal model.
    NeuroImage 06/2014; · 6.25 Impact Factor
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    ABSTRACT: Aim: To establish normal ranges of maternal placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PlGF ratio at 32-41 weeks' gestation and to evaluate the influence of maternal characteristics, and of fetoplacental Doppler. Material and Methods: Serum levels of PlGF, sFlt-1 and sFlt-1/PlGF ratio were measured in 300 noncomplicated pregnancies (30 at each gestational week between 32 and 41). Quantile regression analysis was used to derive gestational age (GA)-adjusted normal ranges, and to account for characteristics that might influence serum levels. The relationship with Doppler indices was tested, including umbilical artery pulsatility index and middle cerebral artery pulsatility index. Results: PlGF decreased with GA from 32 weeks, while sFlt-1 and sFlt-1/PlGF ratio increased steadily. None of the factors evaluated showed any significant influence on the levels of angiogenic factors. PlGF multiple of the median significantly correlated with mean uterine artery Doppler (R -0.17; p = 0.029). Conclusions: In normal pregnancies during the third trimester, serum PlGF decreases, sFlt-1 increases and sFlt-1/PlGF ratio increases with GA. Angiogenic factor levels needed no adjustment for factors such as smoking, body mass index, blood pressure or parity. © 2014 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 05/2014; · 1.90 Impact Factor
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    ABSTRACT: We explore the possibility of detecting and characterizing the warp of the stellar disc of our Galaxy using synthetic Gaia data. The availability of proper motions and, for the brightest stars radial velocities, adds a new dimension to this study. A family of Great Circle Cell Counts (GC3) methods is used. They are ideally suited to find the tilt and twist of a collection of rings, which allow us to detect and measure the warp parameters. To test them, we use random realizations of test particles which evolve in a realistic Galactic potential warped adiabatically to various final configurations. In some cases a twist is introduced additionally. The Gaia selection function, its errors model and a realistic 3D extinction map are applied to mimic three tracer populations: OB, A and Red Clump stars. We show how the use of kinematics improves the accuracy in the recovery of the warp parameters. The OB stars are demonstrated to be the best tracers determining the tilt angle with accuracy better than $\sim0.5$ up to Galactocentric distance of $\sim16$ kpc. Using data with good astrometric quality, the same accuracy is obtained for A type stars up to $\sim13$ kpc and for Red Clump up to the expected stellar cut-off. Using OB stars the twist angle is recovered to within $< 3^\circ$ for all distances.
    Monthly Notices of the Royal Astronomical Society 05/2014; 442(4). · 5.52 Impact Factor
  • Stefan Savchev, Francesc Figueras, Eduard Gratacos
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    ABSTRACT: Objective: To provide a snapshot of the current trends in managing intrauterine growth restriction (IUGR) and to assess the agreement on the gestational age and the way of delivery in different clinical scenarios. Methods: A PubMed search was performed to identify all original articles on IUGR in the last 6 years. The most active 20 authors were selected as experts and were invited to respond to a survey on their preferred gestational age for elective delivery in several IUGR cases depending on Doppler measurements (including umbilical artery (UA), middle cerebral artery, cerebroplacental ratio, uterine artery and ductus venosus), biophysical profile and cardiotocography. Results: 15 of the 20 selected experts agreed to participate in the survey, of which 3 failed to meet the deadline to complete the survey. Management of IUGR was relatively uniform for abnormal UA, uterine artery or cerebroplacental ratio. Although average gestational age at delivery reflected a clear progression with accepted markers of severity, discrepancies of up to 4 weeks were found for abnormal middle cerebral artery Doppler and absent end-diastolic velocity in the UA, and of up to 8 weeks for reverse end-diastolic velocity in the UA and abnormalities in the ductus venosus Doppler. Conclusions: Management of IUGR is still far from being uniform among centers, with most controversy surrounding the management of early-onset IUGR. There is a need of prospective studies to address this issue. © 2014 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 05/2014; · 1.90 Impact Factor
  • Francesc Figueras, Eduard Gratacós
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    ABSTRACT: FGR is among the obstetrical entities with the greatest variation in clinical practice. The first clinically relevant step in the management of fetal growth restriction (FGR) is the distinction of "true" FGR, associated with signs of abnormal feto-placental function and poorer perinatal outcome, from small-for-gestational age (SGA) fetuses, which do not present abnormal Doppler and have near normal perinatal outcome. Such distinction should not be only relied on umbilical artery Doppler, since this parameter identifies only severe, early-onset, forms of placental insufficiency. Instead, FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio, uterine artery Doppler, a growth centile below the 3rd centile. Upon diagnosis, differentiating into early-onset and late-onset FGR is useful to distinguish two clear phenotypes, with differences in severity, association with preeclampsia, and sequence of fetal deterioration. Finally, management of FGR aims at an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. We propose a protocol that integrates current evidence to classify stages of fetal deterioration, and establishes follow-up intervals and optimal delivery timings, which may facilitate decision-making and minimize variability in the clinical management. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 05/2014; · 2.68 Impact Factor
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    ABSTRACT: Objective To investigate whether signs of placental underperfusion (PUP), defined as any maternal and/or fetal vascular pathology, confer a higher risk of neonatal morbidity in late-onset small for gestational age (SGA) fetuses with normal umbilical artery Doppler.MethodsA cohort of 126 SGA singleton fetuses with normal umbilical artery Doppler delivered after 34 weeks was created. For each case, the placenta was histologically evaluated for signs of PUP using a hierarchical and standardized classification system. Neonatal morbidity was assessed by calculation of the morbidity assessment index for newborns (MAIN) score, a validated outcome scale. The independent association between PUP and neonatal morbidity was evaluated using multivariable median regression.ResultsIn a total of 84 placentas (66.7%), there were 97 placental histological findings that qualified as signs of PUP. These cases had a significantly higher incidence of emergent delivery for non-reassuring fetal status (44.1% vs. 21.4%; p=0.013) and neonatal metabolic acidosis at birth (33.3% vs. 14.3%; p=0.023). The median MAIN score significantly differed between groups (89 vs. 0; p=0.025). This difference remained significant after adjustment for potential confounders. The proportion of cases with mild to severe morbidity scores was also significantly higher in the PUP group (31% vs. 14.3%; p=0.043).Conclusion In late-onset SGA with normal umbilical artery Doppler, signs of PUP confer higher neonatal morbidity. These findings allow phenotypic profiling of fetal growth restriction among the general population of late-onset SGA.
    Ultrasound in Obstetrics and Gynecology 05/2014; · 3.56 Impact Factor
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    ABSTRACT: Maternal residential proximity to roads has been associated with adverse pregnancy outcomes. However, there is no study investigating mediators or buffering effects of road-adjacent trees on this association. We investigated the association between mothers' residential proximity to major roads and term low birth weight (LBW), while exploring possible mediating roles of air pollution (PM2.5, PM2.5-10, PM10, PM2.5 absorbance, nitrogen dioxide, and nitrogen oxides), heat, and noise and buffering effect of road-adjacent trees on this association. This cohort study was based on 6438 singleton term births in Barcelona, Spain (2001-2005). Road proximity was measured as both continuous distance to and living within 200 m from a major road. We assessed individual exposures to air pollution, noise, and heat using, respectively, temporally adjusted land-use regression models, annual averages of 24-hour noise levels across 50 m and 250 m, and average of satellite-derived land-surface temperature in a 50-m buffer around each residential address. We used vegetation continuous fields to abstract tree coverage in a 200-m buffer around major roads. Living within 200 m of major roads was associated with a 46% increase in term LBW risk; an interquartile range increase in heat exposure with an 18% increase; and third-trimester exposure to PM2.5, PM2.5-10, and PM10 with 24%, 25%, and 26% increases, respectively. Air pollution and heat exposures together explained about one-third of the association between residential proximity to major roads and term LBW. Our observations on the buffering of this association by road-adjacent trees were not consistent between our 2 measures of proximity to major roads. An increased risk of term LBW associated with proximity to major roads was partly mediated by air pollution and heat exposures.
    Epidemiology (Cambridge, Mass.) 04/2014; · 5.51 Impact Factor
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    ABSTRACT: Objective: To explore the predictive role of angiogenic factors for the prediction of early and late preeclampsia (PE) in the first trimester. Methods: A nested case-control study, within a cohort of 5,759 pregnancies, including 28 cases of early, 84 of late PE (cut-off 34 weeks) and 84 controls. Maternal characteristics, mean blood pressure (MAP), uterine artery (UtA) Doppler (11-13 weeks), vascular endothelial growth factor, placental growth factor (PlGF), soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (8-11 weeks) were measured/recorded. All parameters were normalized by logarithmic transformation; logistic regression analysis was used to predict PE. Results: For early PE, significant contributions were chronic hypertension, previous PE, MAP, UtA Doppler, PlGF and sFlt-1. A model including these predictors achieved detection rates (DR) of 77.8 and 88.9% for 5 and 10% false-positive rates (FPR), respectively (AUC 0.958; 95% CI 0.920-0.996). For late PE, significant contributions were provided by body mass index, previous PE, UtA Doppler, PlGF and sFlt-1. The model including these factors achieved DR of 51.2 and 69% at 5 and 10% FPR, respectively (AUC 0.888; 95% CI 0.840-0.936). Conclusions: Among angiogenic factors, not only PlGF but also sFlt-1 substantially improve the prediction for early and late PE. The data need confirmation in larger studies. © 2014 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 04/2014; · 1.90 Impact Factor
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    ABSTRACT: This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP). In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters. A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p = 0.008). Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates. Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.
    Placenta 04/2014; · 3.12 Impact Factor
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    ABSTRACT: Objective To evaluate corpus callosum (CC) development by Magnetic Resonance Imaging (MRI) in late-onset intrauterine growth restricted (IUGR) fetuses compared to appropriatefor gestational age (AGA) and its association with neurobehavioral outcome.Method117 late-onset IUGR and 73 control fetuses were imaged using a 3 T MRI scanner at term, obtaining T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE) anatomical slices. CC length, thickness, total area and the areas after a subdivision in 7 portions were assessed. Neonatal Behavioral Assessment Scale (NBAS) test was performed on IUGR newborns at 42 ± 1 weeks.ResultsIUGR fetuses showed significantly smaller CC (Total CC Area IUGR: 1.3996 ± 0.26 vs. AGA: 1.664 ± 0.31; p < 0.01) and smaller subdivision areas as compared with controls. The differences were slightly more pronounced in fetuses with very low birth weight and abnormal brain or uterine Doppler. CC measurements were significantly associated with neurobehavioral outcome in IUGR cases.ConclusionsCC development was significantly altered in late-onset IUGR fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 04/2014; · 2.68 Impact Factor

Publication Stats

2k Citations
1,074.85 Total Impact Points


  • 2009–2014
    • Centro de Investigación Biomédica en Red de Enfermedades Raras
      Valenza, Valencia, Spain
    • Society for Maternal-Fetal Medicine
      Santa Maria, California, United States
  • 2007–2014
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 1999–2014
    • Hospital Clínic de Barcelona
      • • Servicio de Medicina Materno Fetal
      • • Servicio de Medicina Nuclear
      Barcino, Catalonia, Spain
  • 1985–2014
    • University of Barcelona
      • • Department of Obstetrics and Gynecology, Pediatrics, Radiology and Anatomy
      • • Departament d'Astronomia i Meteorologia
      Barcino, Catalonia, Spain
  • 2011–2013
    • CREAL Center for Research in Environmental Epidemiology
      Barcino, Catalonia, Spain
  • 2010
    • Aga Khan University Hospital, Karachi
      Kurrachee, Sindh, Pakistan
  • 2007–2010
    • Perinatal Institute
      Birmingham, England, United Kingdom
  • 2008
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 2004–2006
    • Southern Medical Clinic
      San Fernando, City of San Fernando, Trinidad and Tobago
  • 2005
    • University Hospital Vall d'Hebron
      • Department of Obstetrics
      Barcino, Catalonia, Spain
  • 1999–2003
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
  • 1984
    • Central University of Venezuela
      Caracas, Distrito Federal, Venezuela