Articles publicats en revistes (BCNatal Fetal Medicine Research Center)

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Maternal stress, anxiety, well-being, and sleep quality in pregnant women throughout gestation
(MDPI, 2023-11-26) Martín Asuero, Andrés; Pascal Capdevila, Rosalia; Casas, Irene; Genero, Mariona; Nakaki, Ayako; Youssef, Lina; Larroya, Marta; Benitez, Leticia; Gomez, Yvan; Martínez-Arán, Anabel, 1971-; Morilla, Ivette; Oller-Guzmán, Teresa M.; Vieta i Pascual, Eduard, 1963-; Crispi Brillas, Fàtima; Gratacos, Eduard; Gómez Roig, Ma. Dolores; Crovetto, Francesca
Background: Maternal stress, anxiety, well-being, and sleep quality during pregnancy have been described as influencing factors during pregnancy. Aim: We aimed to describe maternal stress, anxiety, well-being, and sleep quality in pregnant women throughout gestation and their related factors. Methods: A prospective study including pregnant women attending BCNatal, in Barcelona, Spain (n = 630). Maternal stress and anxiety were assessed by the Perceived Stress Scale (PSS) and State-Trait Anxiety Inventory (STAI)-validated questionnaires. Maternal well-being was assessed using theWorld Health OrganizationWell-Being Index Questionnaire (WHO-5), and sleep quality was assessed using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). All questionnaires were obtained twice during the second and third trimester of pregnancy. A multivariate analysis was conducted to assess factors related to higher maternal stress and anxiety and worse well-being and sleep quality. Results: High levels of maternal stress were reported in 23.1% of participants at the end of pregnancy, with maternal age <40 years (OR 2.02; 95% CI 1.08–3.81, p = 0.03), non-white ethnicity (OR 2.09; 95% CI 1.19–4.02, p = 0.01), and non-university studies (OR 1.86; 95% CI 1.08–3.19, p = 0.02) being the parameters mostly associated with it. A total of 20.7% of women had high levels of anxiety in the third trimester and the presence of psychiatric disorders (OR 3.62; 95% CI 1.34–9.78, p = 0.01) and non-university studies (OR 1.70; 95% CI 1.11–2.59, p = 0.01) provided a significant contribution to high anxiety at multivariate analysis. Poor maternal well-being was observed in 26.5% of women and a significant contribution was provided by the presence of psychiatric disorders (OR 2.96; 95% CI 1.07–8.25, p = 0.04) and non-university studies (OR 1.74; 95% CI 1.10–2.74, p = 0.02). Finally, less sleep quality was observed at the end of pregnancy (p < 0.001), with 81.1% of women reporting poor sleep quality. Conclusion: Maternal stress and anxiety, compromised maternal well-being, and sleep quality disturbances are prevalent throughout pregnancy. Anxiety and compromised sleep quality may increase over gestation. The screening of these conditions at different stages of pregnancy and awareness of the associated risk factors can help to identify women at potential risk.
Prenatal exposure to per- and polyfluoroalkyl substances, fetoplacental hemodynamics, and fetal growth
(Elsevier Ltd., 2024-11-06) Cserbik, Dora; Knox, Bethany; Güil-Oumrait, Nuria; Basagaña, Xavier; Dadvand, Payam; Foraster, Maria; Galmes, Toni; Gascón, Mireia; Gómez Roig, Ma. Dolores; Gómez-Herrera, Laura; Småstuen Haug, Line; Llurba Olivé, Elisa; Márquez, Sandra; Rivas, Ioar; Sunyer, Jordi; Thomsen, Cathrine; Zanini, Maria Julia; Bustamante Pineda, Mariona; Vrijheid, Martine
Introduction: The impact of legacy per- and polyfluoroalkyl substances (PFAS) on fetal growth has been well studied, but assessments of next-generation PFAS and PFAS mixtures are sparse and the potential role of fetoplacental hemodynamics has not been studied. We aimed to evaluate associations between prenatal PFAS exposure and fetal growth and fetoplacental hemodynamics. Methods: We included 747 pregnant women from the BiSC birth cohort (Barcelona, Spain (2018-2021)). Twenty-three PFAS were measured at 32 weeks of pregnancy in maternal plasma, of which 13 were present above detectable levels. Fetal growth was measured by ultrasound, as estimated fetal weight at 32 and 37 weeks of gestation, and weight at birth. Doppler ultrasound measurements for uterine (UtA), umbilical (UmA), and middle cerebral artery (MCA) pulsatility indices (PI), as well as the cerebroplacental ratio (CPR - ratio MCA to UmA), were obtained at 32 weeks to assess fetoplacental hemodynamics. We applied linear mixed effects models to assess the association between singular PFAS and longitudinal fetal growth and PI, and Bayesian Weighted Quantile Sum models to evaluate associations between the PFAS mixture and the aforementioned outcomes, controlled for the relevant covariates. Results: Single PFAS and the mixture tended to be associated with reduced fetal growth and CPR PI, but few associations reached statistical significance. Legacy PFAS PFOS, PFHpA, and PFDoDa were associated with statistically significant decreases in fetal weight z-score of 0.13 (95%CI (-0.22, -0.04), 0.06 (-0.10, 0.01), and 0.05 (-0.10, 0.00), respectively, per doubling of concentration. The PFAS mixture was associated with a non-statistically significant 0.09 decrease in birth weight z-score (95%CI -0.22, 0.04) per quartile increase. Conclusion: This study suggests that legacy PFAS may be associated with reduced fetal growth, but associations for next generation PFAS and for the PFAS mixture were less conclusive. Associations between PFAS and fetoplacental hemodynamics warrant further investigation.
Machine learning-driven blood biomarker profiling and EGCG intervention in fetal alcohol spectrum disorder
(Elsevier España, 2025-09-04) Ramos-Triguero, Anna; Navarro Tapia, Elisabet; Vieiros, Melina; Martínez, Leopoldo; García Algar, Óscar; Andreu Fernández, Vicente
Fetal alcohol spectrum disorders (FASD) is a complex neurodevelopmental condition caused by prenatal alcohol exposure (PAE), often underdiagnosed due to heterogeneous symptoms and diagnostic challenges. This study aimed to identify serum-based biomarkers for early FASD diagnosis and assess the potential of epigallocatechin gallate (EGCG), a natural antioxidant found in green tea, in modulating markers related to FASD. Luminex immunoassays were employed to analyze serum samples from FASD patients, identifying seven predictive biomarkers involved in neuroinflammation and immune dysregulation: IL-10, IFNγ, CCL2, NGFβ, IL-1β, CX3CL1, and CXCL16. These biomarkers reflect key disruptions in brain health, particularly in neuroinflammation, which contributes to the cognitive, behavioral, and mental health challenges frequently observed in FASD patients, including memory deficits, attention problems, and emotional dysregulation. To enhance diagnostic precision, machine learning (ML) models were trained on these biomarker datasets, with Random Forest (RF) achieving the highest accuracy (0.89), sensitivity (0.92), specificity (0.83), and ROC AUC (0.88). Additionally, an open-label pilot study in children diagnosed with FASD showed significant restoration of the levels of IFNy, CX3CL1, IL-1β, IL-10, and NGFβ after 12 months of EGCG treatment, suggesting its potential role in mitigating neuroinflammatory responses and promoting neurogenesis. These findings underscore the value of integrating serum biomarkers with ML-driven approaches to advance FASD diagnostics, while also identifying EGCG as a promising intervention for neurodevelopmental and mental health impairments associated with the disorder.
The frequency-following response (FFR) in late preterm neonates: a pilot study
(Frontiers Media, 2024-05-09) Ribas-Prats, Teresa; Arenillas-Alcón, Sonia; Ferrero Martínez, Silvia; Gómez Roig, Ma. Dolores; Escera i Micó, Carles
Introduction: Infants born very early preterm are at high risk of language delays. However, less is known about the consequences of late prematurity. Hence, the aim of the present study is to characterize the neural encoding of speech sounds in late preterm neonates in comparison with those born at term. Methods: The speech-evoked frequency-following response (FFR) was recorded to a consonant-vowel stimulus /da/ in 36 neonates in three different groups: 12 preterm neonates [mean gestational age (GA) 36.05 weeks], 12 “early term neonates” (mean GA 38.3 weeks), and “late term neonates” (mean GA 41.01 weeks). Results: From the FFR recordings, a delayed neural response and a weaker stimulus F0 encoding in premature neonates compared to neonates born at term was observed. No differences in the response time onset nor in stimulus F0 encoding were observed between the two groups of neonates born at term. No differences between the three groups were observed in the neural encoding of the stimulus temporal fine structure. Discussion: These results highlight alterations in the neural encoding of speech sounds related to prematurity, which were present for the stimulus F0 but not for its temporal fine structure.
Effects of Antioxidant Intake on Fetal Development and Maternal/Neonatal Health during Pregnancy.
(MDPI, 2022-03-28) Sebastiani, Giorgia; Navarro Tapia, Elisabet; Almeida Toledano, Laura; Serra Delgado, Mariona; Paltrinieri, Anna Lucia; García Algar, Óscar; Andreu Fernández, Vicente
During pregnancy, cycles of hypoxia and oxidative stress play a key role in the proper development of the fetus. Hypoxia during the first weeks is crucial for placental development, while the increase in oxygen due to the influx of maternal blood stimulates endothelial growth and angiogenesis. However, an imbalance in the number of oxidative molecules due to endogenous or exogenous factors can overwhelm defense systems and lead to excessive production of reactive oxygen species (ROS). Many pregnancy complications, generated by systemic inflammation and placental vasoconstriction, such as preeclampsia (PE), fetal growth restriction (FGR) and preterm birth (PTB), are related to this increase of ROS. Antioxidants may be a promising tool in this population. However, clinical evidence on their use, especially those of natural origin, is scarce and controversial. Following PRISMA methodology, the current review addresses the use of natural antioxidants, such as epigallocatechin gallate (EGCG), melatonin and resveratrol (RESV), as well as other classical antioxidants (vitamin C and E) during the prenatal period as treatment of the above-mentioned complications. We review the effect of antioxidant supplementation on breast milk in lactating mothers.
Effects of maternal drinking patterns and epigallocatechin-3-gallate treatment on behavioural and molecular outcomes in a mouse model of fetal alcohol spectrum disorders
(Elsevier Masson SAS, 2025-05-10) Vieiros, Melina; Almeida Toledano, Laura; Serra Delgado, Mariona; Navarro Tapia, Elisabet; Ramos-Triguero, Anna; Muñoz Lozano, Concha; Martínez Martínez, Leopoldo; Marchei, Emilia; Gómez Roig, Ma. Dolores; García Algar, Óscar; Andreu Fernández, Vicente
Prenatal alcohol exposure (PAE) impairs fetal development leading to fetal alcohol spectrum disorders (FASD). Antioxidants like epigallocatechin-3-gallate (EGCG) may mitigate alcohol-induced oxidative stress, a major contributor to FASD. This study assessed the effects of PAE on cognition and behaviour under two drinking patterns and the role of postnatal EGCG therapy in a FASD-like mouse model. C57BL/6J mice were divided into five groups: control, moderate drinking (Mod), binge drinking (Bin), Mod+EGCG, and Bin+EGCG. Cognitive and behavioural performance were assessed using Rotarod test, T-Maze, and Morris Water Maze (MWM). Western blot analyses evaluated brain and cerebellum biomarkers related to neuronal plasticity, maturation, differentiation, transport, and proliferation. PAE impaired motor coordination, significantly reducing rotarod walking time in both drinking patterns. Spatial learning and memory were also disrupted, decreasing T-maze success rate. It also decreased time in the platform area and distance travelled in MWM. Both drinking patterns affected neuronal plasticity (BDNF, DYRK1A) and maturation (NeuN), astrocyte differentiation (GFAP, s100β), neuronal transport (MBP) and proliferation (GDNF, Wnt-3) via oxidative stress (Nrf2). Our results show how EGCG treatment significantly improved behavioural tests results and restored most brain and cerebellum biomarkers, reaching levels similar to control. These findings highlight the impact of PAE on cognition and behaviour and how EGCG may counteract its effects by reducing oxidative stress and enhancing brain plasticity. Our findings open the door to future studies on the mechanism of action of this antioxidant in order to use it as a therapeutic tool in this vulnerable population.
Mortality and severe neurological morbidity in extremely preterm fetal growth-restricted fetuses
(John Wiley & Sons, 2023-12) Mazarico Gallego, Edurne; Meler Barrabés, Eva; Mendoza Cobaleda, Manel; Herraiz, Ignacio; Llurba Olivé, Elisa; De Diego, Raúl; Comas Rovira, Montserrat; Boada, David; González Cammareri, Anna; Bonacina, Erika; Armengol Alsina, Mireia; Moline, Elisenda; Hurtado, Ivan; Torre, Núria; Gómez Roig, Ma. Dolores; Galindo Izquierdo, Alberto; Figueras, Francesc
Objective: To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. Methods: This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. Results: A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. Conclusions: Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
External validation of a non-invasive vaginal tool to assess the risk of intra-amniotic inflammation in pregnant women with preterm labor and intact membranes
(Walter de Gruyter, 2024) Cobo Cobo, María Teresa; Burgos Artizzu, Xavier P.; Ferrero Martínez, Silvia; Balcells, Judith; Bosch, Jaime; Gené, Amadeu; Murillo Bravo, Clara; Rueda, Claudia; Boada, David; Sánchez Antón, Maria Teresa; Kacerovsky, Marian; Jacobsson, Bo; Palacio, Montse
Objectives: To prospectively validate the diagnostic performance of a non-invasive point-of-care tool (Rapid IAI System), including vaginal alpha-fetoprotein and interleukin-6, to predict the occurrence of intra-amniotic inflammation in a Spanish cohort of patients admitted with a diagnosis of preterm labor and intact membranes. Methods: From 2017 to 2022, we prospectively evaluated a cohort of pregnant women diagnosed with preterm labor and intact membranes admitted below 34+0 weeks who underwent amniocentesis to rule-in/out intra-amniotic infection and/or inflammation. Vaginal sampling was performed at the time of amniocentesis or within 24-48 h. Amniotic fluid IL-6, vaginal alpha-fetoprotein and vaginal IL-6 concentrations were measured using a point-of-care tool provided by Hologic Inc., "Rapid IAI System". We defined intra-amniotic inflammation when amniotic fluid IL-6 values were greater than 11.3 ng/mL. During recruitment, clinicians were blinded to the results of the point-of-care tool. The original prediction model proposed by Hologic Inc. to predict intra-amniotic inflammation was validated in this cohort of patients. Results: We included 151 patients diagnosed with preterm labor and intact membranes. Among these, 29 (19.2 %) had intra-amniotic inflammation. The algorithm including vaginal IL-6 and alpha-fetoprotein showed an area under curve to predict intra-amniotic inflammation of 80.3 % (±5.3 %) with a sensitivity of 72.4 %, specificity of 84.6 %, positive predictive valuve (PPV) of 52.5 %, negative predictive value (NPV) of 92.9 %, and a positive likelihood ratio (LR+) of 4.6 and negative likelihood ratio (LR-) of 0.33. Conclusions: External validation of a non-invasive rapid point-of-care tool, including vaginal alpha-fetoprotein and IL-6, showed very good diagnostic performance for predicting the absence of intra-amniotic inflammation in women with preterm labor and intact membranes.
A Rapid Amniotic Fluid Interleukin-6 Assessment for the Identification of Intra-Amniotic Inflammation in Women with Preterm Labor and Intact Membranes
(Karger, 2021-06-01) Cobo, Teresa; Aldecoa, Victoria; Holeckova, Magdalena; Andrys, Ctirad; Filella Pla, Xavier; Jacobsson, Bo; Kacerovsky, Marian
Objectives: A multivariable predictive model has recently been developed with good accuracy to predict spontaneous preterm delivery within 7 days in women with preterm labor (PTL) and intact membranes. However, this model measures amniotic fluid (AF) interleukin (IL)-6 concentrations using the ELISA method, thereby limiting clinical implementation. The main objectives of this study were to validate the automated immunoassay as a quantitative method to measure AF IL-6 in women with PTL and to evaluate the diagnostic performance of AF IL-6 alone and as part of a multivariable predictive model to predict spontaneous delivery in 7 days with this automated method. Study design: This is a retrospective observational study in women with PTL below 34 weeks who underwent amniocentesis to rule out microbial invasion of the amniotic cavity. Women with clinical signs of chorioamnionitis, cervical length measurement at admission >5th centile, maternal age <18 years, and no consent to perform amniocentesis for this indication were excluded. The local Institutional Review Boards approved the study (HCB/2019/0940). Analysis of AF IL-6 Concentrations: AF IL-6 concentrations were measured using an automated Cobas e602 electrochemiluminescence immunoanalyzer and Human IL-6 Quantikine ELISA kit. Results: Of the entire study group (n = 100), 38 women spontaneously delivered within 7 days after admission. Both laboratory methods showed good agreement (intraclass correlation coefficient: 0.937 (95% confidence interval [CI] 0.908-0.957); p < 0.001). Diagnostic performance of AF IL-6 to predict spontaneous delivery within 7 days when it was included in the multivariable predictive model showed an area under the receiver operating characteristic curve of 0.894 (95% CI 0.799-0.955), sensitivity of 97%, specificity of 74%, positive predictive value of 73%, negative predictive value of 97%, positive likelihood ratio (LR) of 3.7, and negative LR of 0.045. Conclusion: While both analytical methods were comparable for measuring AF IL-6 concentrations in women with PTL, the Cobas immunoanalyzer provided rapid diagnosis of intra-amniotic inflammation within minutes. The predictive model showed a good diagnostic performance to target women at high risk of spontaneous delivery within 7 days.
Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes.
(Elsevier, 2024-01-09) Murillo Bravo, Clara; Rueda Ricarte, Claudia; Larroya Solà, Marta; Boada, David; Grau, Laia; Ponce, Júlia; Herranz Barbero, Ana; Gómez del Rincón, Olga; Ferrero Martínez, Silvia; Andreu Fernández, Vicente; Gratacós Solsona, Eduard; Crispi Brillas, Fàtima; Palacio, Montse; Cobo, Teresa
Background: Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. Objective: We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. Study design: In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. Results: From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. Conclusion: Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.
Acupuncture before planned admission for induction of labor (ACUPUNT study): a randomized controlled trial
(Elsevier Inc., 2024-08-17) Zamora Brito, Montserrat; Migliorelli, Federico; Pérez Guervós, Raquel; Solans Oliva, Rosa; Arranz Betegón, Ángela; Palacio, Montse
Background: The increase in the use of induction of labor is a worldwide phenomenon in the current management of labor and delivery in Western societies, with approximately one out of every 4 pregnancies undergoing this procedure This has led women to seek various methods for stimulation of the onset of labor. Some data suggest that the use of acupuncture for favoring spontaneous labor onset could reduce the number of inductions of labor procedures. However, good quality evidence in this respect is not yet available. Objective: The aim of this study was to evaluate the effectiveness of acupuncture using a filiform needle to induce spontaneous onset of labor in women with a scheduled induction of labor date and assess the safety and satisfaction of women undergoing acupuncture. Study design: We conducted a multicenter, randomized, controlled, parallel-arm, unmasked trial in 3 hospitals in Spain. Eligible participants were women older than 18 years with a singleton pregnancy and a cephalic presentation, scheduled for induction of labor following center-specific protocols. Participants were randomly allocated to one of 2 groups: the intervention group, which underwent acupuncture sessions for a maximum of 4 days prior to the scheduled induction of labor, or the control group, which received no specific prelabor intervention. The primary study outcome was the proportion of women admitted because of spontaneous onset of labor or premature rupture of membranes before or the day of the scheduled induction of labor. Results: Between November 2017 and June 2023, 212 women were recruited and included in the analysis (106 in the acupuncture group and 106 in the control group). There were no significant differences between the 2 groups in the baseline demographic characteristics. Regarding the primary outcome, 65.1% (69/106) of women in the acupuncture group and 39.6% (42/106) in the control group were admitted for spontaneous onset of labor or premature rupture of membranes (P<.001). Overall, women in the intervention group were admitted 1.25 days before (SD 1.4) their scheduled induction of labor date compared to 0.67 days (SD 1.15) for those in the control group (P=.001). The median time from recruitment to hospitalization was 4.48 days for the acupuncture group and 5.33 days for the control group (HR 0.52, 95% CI 0.35-0.77, P=.001). There were no significant differences between the 2 groups regarding the time from admission to delivery or the cesarean delivery rate. Nor were there differences in the rates of maternal or neonatal outcomes, and no maternal or fetal deaths occurred in either group. Conclusion: Acupuncture with filiform needles, administered 4 days prior to scheduled induction of labor increased admission for spontaneous onset of labor and premature rupture of membranes before the induction of labor date.
in vivo Monitoring with micro-implantable hypoxia sensor based on tissue acidosis
(Elsevier B.V., 2021-05-01) Dulay, Samuel; Rivas, Lourdes; Miserere, Sandrine; Pla, Laura; Berdún, Sergio; Parra, Johanna; Eixarch Roca, Elisenda; Gratacós Solsona, Eduard; Illa, Míriam; Mir Llorente, Mònica; Samitier i Martí, Josep
Hypoxia is a common medical problem, sometimes difficult to detect and caused by different situations. Control of hypoxia is of great medical importance and early detection is essential to prevent life threatening complications. However, the few current methods are invasive, expensive, and risky. Thus, the development of reliable and accurate sensors for the continuous monitoring of hypoxia is of vital importance for clinical monitoring. Herein, we report an implantable sensor to address these needs. The developed device is a low-cost, miniaturised implantable electrochemical sensor for monitoring hypoxia in tissue by means of pH detection. This technology is based on protonation/deprotonation of polypyrrole conductive polymer. The sensor was optimized in vitro and tested in vivo intramuscularly and ex vivo in blood in adult rabbits with respiration-induced hypoxia and correlated with the standard device ePOCTM. The sensor demonstrated excellent sensitivity and reproducibility; 46.4 ± 0.4 mV/pH in the pH range of 4–9 and the selectivity coefficient exhibited low interference activity in vitro. The device was linear (R2 = 0.925) with a low dispersion of the values (n = 11) with a cut-off of 7.1 for hypoxia in vivo and ex vivo. Statistics with one-way ANOVA (α = 0.05), shows statistical differences between hypoxia and normoxia states and the good performance of the pH sensor, which demonstrated good agreement with the standard device. The sensor was stable and functional after 18 months. The excellent results demonstrated the feasibility of the sensors in real-time monitoring of intramuscular tissue and blood for medical applications.
Longitudinal evolution of central nervous system anomalies in fetuses with open spina bifida fetoscopic repair and correlation with neurologic outcome
(2023-06-01) Trigo, Lucas; Eixarch Roca, Elisenda; Faig Leite, Fernanda; Gómez Chiari, Marta; Rebollo Polo, Mónica; Dalaqua, Mariana; Gratacós Solsona, Eduard; Lapa, Denise Araújo
Background: Open spina bifida is associated with central nervous system anomalies such as abnormal corpus callosum and heterotopias. However, the impact of prenatal surgery over these structures remains unclear. Objective: This study aimed to describe longitudinal changes of central nervous system anomalies before and after prenatal open spina bifida repair and to evaluate their relationship with postnatal neurologic outcomes. Study design: Retrospective cohort study of fetuses with open spina bifida who underwent percutaneous fetoscopic repair from January 2009 to August 2020. All women had presurgical and postsurgical fetal magnetic resonance imaging, at an average of 1 week before and 4 weeks after surgery, respectively. We evaluated defect characteristics in the presurgical magnetic resonance images; and fetal head biometry, clivus supraocciput angle, and the presence of structural central nervous system anomalies, such as abnormalities in corpus callosum, heterotopias, ventriculomegaly, and hindbrain herniation, in both presurgical and postsurgical magnetic resonance images. Neurologic assessment was performed using the Pediatric Evaluation of Disability Inventory scale in children who were 12 months or older, covering 3 different sections, namely self-care, mobility, and social and cognitive function. Results: A total of 46 fetuses were evaluated. Presurgery and postsurgery magnetic resonance imaging were performed at a median gestational age of 25.3 and 30.6 weeks, with a median interval of 0.8 weeks before surgery, and 4.0 weeks after surgery. There was a 70% reduction in hindbrain herniation (100% vs 32.6%; P<.001), and a normalization of the clivus supraocciput angle after surgery (55.3 [48.8-61.0] vs 79.9 [75.2-85.4]; P<.001). No significant increase in abnormal corpus callosum (50.0% vs 58.7%; P=.157) or heterotopia (10.8% vs 13.0%; P=.706) was observed. Ventricular dilation was higher after surgery (15.6 [12.7-18.1] vs 18.8 [13.7-22.9] mm; P<.001), with a higher proportion of severe ventricular dilation after surgery (≥15mm) (52.2% vs 67.4%; P=.020). Thirty-four children underwent neurologic assessment, with 50% presenting a global optimal Pediatric Evaluation of Disability Inventory result and 100% presenting a normal social and cognitive function. Children with optimal global Pediatric Evaluation of Disability Inventory presented a lower rate of presurgical anomalies in corpus callosum and severe ventriculomegaly. When analyzed as independent variables to global Pediatric Evaluation of Disability Inventory scale, the presence of abnormal corpus callosum and severe ventriculomegaly showed an odds ratio of 27.7 (P=.025; 95% confidence interval, 1.53-500.71) for a suboptimal result. Conclusion: Prenatal open spina bifida repair did not change the proportion of abnormal corpus callosum nor heterotopias after surgery. The combination of presurgical abnormal corpus callosum and severe ventricular dilation (≥15 mm) is associated with an increased risk of suboptimal neurodevelopment.
Revisiting MOMS criteria for prenatal repair of spina bifida: upper gestational-age limit should be raised and assessment of prenatal motor function rather than anatomical level improves prediction of postnatal function
(John Wiley & Sons, 2024-01-01) Trigo, Lucas; Chmait, Ramen H.; Llanes, Arlyn; Catissi, Giulia; Eixarch Roca, Elisenda; Van Speybroeck, Alexander; Lapa, Denise Araújo
Objectives: To determine if the lower-extremity neurological motor function level in fetuses with open spina bifida deteriorates within the 4-week interval between a first prenatal motor assessment at around 22 weeks of gestation and a second evaluation, prior to 'late' prenatal surgery, defined as surgery at 26-28 weeks and, in certain situations, up to 30 weeks, and to assess the association between prenatal presurgical motor-function level, anatomical level of the lesion and postnatal motor-function level. Methods: This was a two-center cohort study of 94 singleton fetuses with open spina bifida which underwent percutaneous repair using the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique between December 2016 and January 2022. All women underwent two prenatal systematic ultrasound evaluations, approximately 4 weeks apart, with the second one being performed less than 1 week before surgery, and one postnatal evaluation via physical examination within 2 months of birth. Motor-function classification was from spinal level T12 to S1, according to key muscle function. Each leg was analyzed separately; in case of discrepancy between the two legs, the worst motor-function level was considered for analysis. Motor-function-level evaluations were compared with each other and with the anatomical level as observed on ultrasound. Independent predictors of a postnatal reduction in motor-function level were assessed using a logistic regression model. Results: Prenatal motor-function level was assessed at a median gestational age of 22.5 (interquartile range (IQR), 20.7-24.3) and 26.7 (IQR, 25.4-27.3) weeks, with a median interval of 4.0 (IQR, 2.4-6.0) weeks. The median gestational age at surgery was 27.0 (IQR, 25.9-27.6) weeks and the postnatal examination was at median age of 0.8 (IQR, 0.3-5.4) months. There was no significant difference in motor-function level between the two prenatal evaluations (P = 0.861). We therefore decided to use the second prenatal evaluation for comparison with postnatal motor function and anatomical level. Overall, prenatal and postnatal motor function evaluations were significantly different from the anatomical level (preoperative assessment, P = 0.0015; postnatal assessment, P = 0.0333). Comparing prenatal with postnatal motor-function level, we found that 87.2% of babies had similar or improved motor function compared with that prior to prenatal surgery. On logistic regression analysis, lower anatomical level of defect and greater difference between anatomical level and prenatal motor-function level were identified as independent predictors of postnatal motor function (odds ratio, 0.237 (95% CI, 0.095-0.588) (P = 0.002) and 3.44 (95% CI, 1.738-6.813) (P < 0.001), respectively). Conclusions: During a 4-week interval between first ultrasound evaluation and late fetal surgical repair of open spina bifida, motor function does not change significantly, suggesting that late repair, ≥ 26 weeks, does not impact negatively on motor-function outcome. Compared with the anatomical level of the lesion, preoperative neurological motor-function assessment via ultrasound is more predictive of postnatal motor function, and should be included in preoperative counseling.
Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm prelabor rupture of membranes.
(2024-04-27) Murillo Bravo, Clara; Eixarch Roca, Elisenda; Rueda Ricarte, Claudia; Larroya Solà, Marta; Boada, David; Grau, Laia; Ponce Vilà, Júlia; Aldecoa, Victoria; Monterde Puente, Elena; Ferrero Martínez, Silvia; Andreu Fernández, Vicente; Arca Díaz, Gemma; Oleaga Zufiría, Laura; Ros, Olga; Hernández, Maria Pilar; Gratacós Solsona, Eduard; Palacio, Montse; Cobo Cobo, María Teresa
Brain injury and poor neurodevelopment have consistently been reported in infants and adults born preterm. These changes occur at least in part prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not with neurosonography in combination with amniotic fluid brain injury biomarkers. To evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm prelabor rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a mediator of risk. In this prospective cohort study, fetal brain remodeling and injury was evaluated by neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm prelabor rupture of membranes between 24.0-34.0 weeks, with (n=41) and without (n=54) intra-amniotic inflammation. Controls for neurosonography were outpatient pregnant patients without preterm labor or preterm prelabor rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm prelabor rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin-6 >13.4 ng/ml in preterm labor and >1.43 ng/ml in preterm prelabor rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. As amniotic fluid brain injury biomarkers we selected neuron-specific enolase, protein S100B and glial fibrillary acidic protein. Data was adjusted for cephalic biometrics, fetal growth centile, fetal sex, non-cephalic presentation and preterm prelabor rupture of membranes at admission. Fetuses from mothers with preterm labor with intact membranes or preterm prelabor rupture of membranes had signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in intra-amniotic inflammation, non- intra-amniotic inflammation and control groups, transcerebellar diameter (median (25th; 75th percentile)) was 32.7mm (29.8; 37.6), 35.3mm (31.2;39.6) and 35.0mm (31.3;38.3), respectively (p=0.019); vermian height was 16.9 mm (15.5 ;19.6), 17.2 mm (16.0;18.9) and 17.1mm (15.7;19.0), respectively (p=0.041). Second, they presented a lower corpus callosum area (0.72mm2 (0.59;0. 81), 0.71mm2 (0.63;0.82) and 0.78mm2 (0.71;0. 91), respectively (p=0.006). Third, they showed a delayed cortical maturation (Sylvian fissure depth / biparietal diameter ratio was 0.14 (0.12;0.16), 0.14 (0.13;0.16) and 0.16 (0.15;0.17), respectively (p<0.001), and right parieto-occipital sulci depth ratio was 0.09 (0.07;0.12), 0.11 (0.09;0.14) and 0.11 (0.09;0.14), respectively (p=0.012)). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm prelabor rupture of membranes, had higher concentrations of neuron-specific enolase (11804.6pg/ml (6213.4;21098.8), 8397.7 pg/ml (3682.1;17398.3) and 2393.7pg/ml (1717.1;3209.3), respectively (p<0.001)); protein S100B (2030.6 pg/ml (993;4883.5), 1070.3pg/ml (365.1-1463.2) and 74.8pg/ml (44.7;93.7), respectively (p<0.001)), and glial fibrillary acidic protein (1.01ng/ml (0.54;3.88), 0.965ng/ml (0.59;2.07) and 0.24mg/ml (0.20;0.28), respectively (p=0.002)). Fetuses with preterm labor with intact membranes or preterm prelabor rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in those with intra-amniotic inflammation.
Postnatal genetic and neurodevelopmental assessment in infants born at term with severely low birth weight of non-placental origin
(John Wiley & Sons, 2023-09-01) Paz y Miño, Fernanda; Pauta, Montse; Meler Barrabés, Eva; Matas, Isabel; Mazarico Gallego, Edurne; Camacho, Araceli; Segura, Maria; Figueras, Francesc; Borrell, Antoni
Objective: To determine the frequency of genetic syndromes and childhood neurodevelopmental impairment in non-malformed infants born at term with severely low birth weight and no evidence of placental insufficiency. Methods: This case series was constructed from the data of infants delivered at term between 2013 and 2018 with severely low birth weight, defined as birth weight more than 2.5 SD below the mean, with normal maternal and fetal Doppler (umbilical artery, fetal middle cerebral artery, cerebroplacental ratio and uterine artery) and no maternal hypertensive disorder during pregnancy or fetal structural anomaly on prenatal ultrasound examination. Clinical exome sequencing and copy number variation (CNV) analysis were performed using DNA extracted from the children's saliva. Cognitive and psychomotor development was evaluated using the Bayley Scales of Infant and Toddler Development, 3rd edition or the Wechsler Intelligence Scale for Children, 5th edition tests, according to the child's age at testing. Results: Among the 36 405 infants born within the study period, 274 (0.75%) had a birth weight below -2.5 SD, of whom 98 met the inclusion criteria. Among the 63 families contacted, seven (11%) reported a postnatal diagnosis of a genetic syndrome and a further 18 consented to participate in the study. Median gestational age at delivery was 38.0 (interquartile range (IQR), 37.3-38.5) weeks and median birth weight was 2020 (IQR, 1908-2248) g. All 18 children showed a normal result on clinical exome sequencing and CNV analysis, but six (33%) obtained a low score on neurodevelopmental testing. Conclusion: Non-malformed severely small term infants with no clinical or Doppler signs of placental insufficiency present a high rate of genetic syndromes and neurodevelopmental impairment during childhood. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
A novel NONO nonsense variant in a fetus with renal abnormalities
(John Wiley & Sons, 2024-01-01) Rodríguez Revenga, Laia; Nadal Serra, Alfons; Borobio, Virginia; Álvarez Mora, María Isabel; Madrigal Bajo, Irene; Pauta, Montse; Borrell, Antoni
At 16 + 6-weeks a fetal scan performed in the second pregnancy of a 42 y.o. woman identified a right multicystic dysplastic kidney, left renal agenesis, absent urinary bladder, myocardial hypertrophy, increased nuchal fold, a single umbilical artery, and oligohydramnios. Trio exome sequencing analysis detected a novel pathogenic NONO variant. Postmortem examination after the termination of pregnancy confirmed the ultrasound findings and also revealed pulmonary hypoplasia, retrognathia and low-set ears. The variant was a novel de novo hemizygous pathogenic loss-of-function variant in NONO [NM_007363.5], associated with a rare X-linked recessive neurodevelopmental disorder, named intellectual developmental disorder, X-linked syndromic 34 (OMIM#300967). The postnatal characteristic features of this disorder include intellectual disability, developmental delay, macrocephaly, structural abnormalities involving the corpus callosum and/or cerebellum, left ventricular noncompaction and other congenital heart defects. In the prenatal setting, the phenotype has been poorly described, with all described cases presenting with heart defects. This case highlights the need of further clinical delineation to include renal abnormalities in the prenatal phenotype spectrum.
Maternal and fetal outcomes of pregnancy in women with primary systemic vasculitis: A single-center cohort study of 20 patients and 30 pregnancies
(Elsevier, 2024-06-01) Beça, Sara; Alba Garibay, Marco Antonio; Hernández Rodríguez, José; Espigol Frigolé, Georgina; Prieto González, Sergio; Cid Xutglà, M. Cinta; Baños, Núria; Espinosa Garriga, Gerard
Objectives: To analyze pregnancy outcomes of patients with primary systemic vasculitis followed in a third-level referral center. Methods: Retrospective cohort study of all pregnant women with systemic vasculitis followed between 2009 and 2022 at the High-Risk Pregnancy Clinic of the Department of Systemic Autoimmune Diseases of the Hospital Clinic, Barcelona. Results: Twenty women with primary vasculitis were identified, with a total of 30 pregnancies. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (n = 7) and Behcet disease (n = 4) were the most frequent types of vasculitis. All women had the diagnosis of vasculitis before pregnancy, with a median time between disease diagnosis and pregnancy of 5.8 years (range: 2 months-29 years). Most were in remission at conception (76.7 %). During pregnancy, a vasculitis flare occurred in 4 (13.3 %) patients (one each with Takayasu arteritis, eosinophilic granulomatosis with polyangiitis [EGPA], IgA vasculitis [IgAV], and Behcet disease [BD]). Four (16.7 %) of the successful pregnancies had post-partum relapses (one each with EGPA, granulomatosis with polyangiitis, IgAV, and BD). Eighty percent of pregnancies resulted in live babies. In four cases (13.3 %), medical termination of pregnancy was decided, considering the mother or baby health risk. There were two spontaneous miscarriages, and no stillbirths or neonatal deaths. Preeclampsia was the most frequent maternal complication (25 %). Newborns were preterm in 24 % and low birthweight in 20 % of cases. No maternal deaths occurred. Conclusions: This cohort study shows that vasculitis relapses during pregnancy and post-partum, together with other pregnancy complications, occur in a considerable number of patients with systemic vasculitides, although a final good pregnancy outcome can be expected in most cases. These findings emphasize the convenience of managing these special situations in expert reference centers.
Cardiac remodeling from the fetus to adulthood
(Wiley, 2023-02-01) Youssef, Lina; Castellani, Roberta; Valenzuela Alcaraz, Brenda I.; Sepúlveda Martínez, Álvaro; Crovetto, Francesca; Crispi Brillas, Fàtima
Prenatal cardiac remodeling refers to in utero changes in the fetal heart that occur as a response to an adverse intrauterine environment. In this article, we will review the main mechanisms leading to cardiac remodeling and dysfunction, summarizing and describing the major pathological conditions that have been reported to be related to this in utero plastic adaptive process. We will also recap the current evidence regarding the persistence of fetal cardiac remodeling and dysfunction, both in infancy and later in adult life. Moreover, we will discuss primary, secondary, and tertiary preventive measures and future clinical and research aspects.
Quantitative ultrasound image analysis of axillary lymph nodes to differentiate malignancy from reactive benign changes due to COVID-19 vaccination
(Elsevier B.V., 2022-09-01) Coronado-Gutiérrez, D.; Ganau, Sergi; Bargalló, Xavier; Úbeda, Belén; Porta, Marta; Sanfeliu, Esther; Burgos Artizzu, Xavier P.
Purpose: The aim of this study is to assess the potential of quantitative image analysis and machine learning techniques to differentiate between malignant lymph nodes and benign lymph nodes affected by reactive changes due to COVID-19 vaccination. Method: In this institutional review board-approved retrospective study, we improved our previously published artificial intelligence model, by retraining it with newly collected images and testing its performance on images containing benign lymph nodes affected by COVID-19 vaccination. All the images were acquired and selected by specialized breast-imaging radiologists and the nature of each node (benign or malignant) was assessed through a strict clinical protocol using ultrasound-guided biopsies. Results: A total of 180 new images from 154 different patients were recruited: 71 images (10 cases and 61 controls) were used to retrain the old model and 109 images (36 cases and 73 controls) were used to evaluate its performance. The achieved accuracy of the proposed method was 92.7% with 77.8% sensitivity and 100% specificity at the optimal cut-off point. In comparison, the visual node inspection made by radiologists from ultrasound images reached 69.7% accuracy with 41.7% sensitivity and 83.6% specificity. Conclusions: The results obtained in this study show the potential of the proposed techniques to differentiate between malignant lymph nodes and benign nodes affected by reactive changes due to COVID-19 vaccination. These techniques could be useful to non-invasively diagnose lymph node status in patients with suspicious reactive nodes, although larger multicenter studies are needed to confirm and validate the results.

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