Pérez Fernández, Virginia

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Pérez Fernández, Virginia

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Pérez Fernández, Virginia

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Universidad de Murcia. Departamento de Ciencias Sociosanitarias

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Open Access
Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort
(Wiley, 2022-02) García-Serna, Azahara M.; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Molina-Ruano, María Dolores; Rojo-Atenza, Encarna; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Ciencias Sociosanitarias
Background: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. Methods: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-β, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. Results: NO2 during the whole pregnancy increased the odds of detection of IL-1β (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. Conclusions: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
Open Access
Cytokine production by newborns: influence of sex and season of birth
(Natureportfolio, 2022-08-09) García-Serna, Azahara M; Cantero-Cano, Ester; Norte-Muñoz, María; Gil-Buendía, M. Ángeles; Velázquez-Marín, Josefa; Martínez-Torres, Antonia E; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Immune signatures at birth could be associated with clinical outcomes and will improve our understanding of immunity prenatal programming. Methods: Data come from 235 newborns from the cohort study NELA. Production of cytokines was determined using Luminex technology. Associations between cytokine concentrations with sex and season of birth were examined by multivariate regression models. Results: Umbilical cord blood cells produced high levels of inflammatory cytokines, moderate levels of Th1/Th2/Tr-related cytokines, and low levels of Th17 cytokines. Compared to females, male newborn cells secreted higher levels of Th2 (peptidoglycan-stimulated IL-13, odds ratio [OR] = 2.26; 95% CI 1.18, 4.31, p value = 0.013) and Th17 (polyinosinic:polycytidylic acid-stimulated IL-23, OR = 1.82, 95% CI 1.01, 3.27, p value = 0.046) and lower levels of Th1 (olive-stimulated IL-2, OR = 0.56, 95% CI 0.31, 0.99, p value = 0.047) cytokines. Also, children born during warm seasons showed decreased innate cytokine response to peptidoglycan (IL-6, OR = 0.28, 95% CI 0.15, 0.52, p value < 0.001) compared to those born in cold seasons; meanwhile, adaptive immunity cytokines were more frequently secreted by children born during warm seasons in response to allergen extracts (IL-10, OR = 2.11, 95% CI 1.12, 3.96, p value = 0.020; IL-17F, OR = 3.31, 95% CI 1.83, 5.99, p value < 0.001). Conclusion: Newborns showed specific cytokines signatures influenced by sex and season of birth. Impact: There is a limited number of population-based studies on the immune status at birth and the influence of prenatal and perinatal factors on it. Characterization of cytokine signatures at birth related to the prenatal environment could improve our understanding of immunity prenatal programming. Newborns exhibit specific unstimulated and stimulated cytokine signatures influenced by sex and season of birth. Unstimulated and stimulated cytokine signatures in newborns may be associated with the development of related clinical outcomes later in life.
Open Access
Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort
(2022-02-18) García-Serna, Azahara M; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Molina-Ruano, María Dolores; Rojo-Atenza, Encarna; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. Methods: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-β, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. Results: NO2 during the whole pregnancy increased the odds of detection of IL-1β (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. Conclusions: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
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Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort
(ELSEVIER, 2021) García-Serna, Azahara M; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Ballesteros-Meseguer, Carmen; Pérez de Los Cobos, Irene; NELA Study group; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. Methods: In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. Results: Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 μg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 μg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 μg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. Conclusions: Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.
Open Access
Los modelos multinivel en el análisis de factores de riesgo de sibilancias recurrentes en lactantes : enfoques frecuentista y bayesiano
(2013-01-16) Pérez Fernández, Virginia; Sánchez-Solís de Querol, Manuel; Pérez Flores, Domingo; Salmerón Martínez, Diego; Departamentos y Servicios::Departamentos de la UMU::Ciencias Sociosanitarias
En esta tesis se han mostrado los conceptos fundamentales de la metodología multinivel, y se han desarrollado los enfoques frecuentista y bayesiano para el análisis de los modelos multinivel logísticos de 2 niveles. Se ha realizado un estudio comparativo entre un método de análisis que no tiene en cuenta la estructura jerárquica de los datos y los métodos multinivel para el análisis de los factores de riesgo de las sibilancias recurrentes en lactantes. Se han comparado los enfoques frecuentista y bayesiano tanto para el análisis de los modelos multinivel de 2 niveles completamente aleatorios, con intercepto y pendiente aleatoria, como para los modelos de 2 niveles con intercepto aleatorio y variables explicativas del primer nivel y del segundo nivel. El resultado obtenido es que los modelos multinivel mejoran la precisión de las estimaciones de los parámetros respecto a los modelos que no tienen en cuenta la estructura jerárquica de los datos.Key Words: Modelos Jerárquicos, Análisis multinivel, Modelos logisticos, Métodos bayesianos, Algoritmo PQL. SUMMARY: This thesis shows the fundamental concepts of the multilevel methodology, and the frequentist and bayesian approaches for multilevel models for binary responses. A comparative study between a method of analysis which does not consider the hierarchical structure of the data and two multilevel methods when applied to study of wheezing and its risk factors in the first year of life. A bayesian and frequentist methods were compared for fitting a two-level random slope model, with random intercept and random slope, and for a random intercept model with a two level explanatory variables. The results show that the multilevel models improve estimations accuracy of parameters regarding models which do not consider the hierarchical structure of the data. Key Words: hierarchical models, contextual analysis, logistic models, Bayesian Methods, PQL estimation.
Open Access
The Nutrition in Early Life and Asthma (NELA) birth cohortstudy: Rationale, design, and methods
Alcantara Lopez, Maria V.; Cabezas Herrera, Juan; Jimenez Guerrero, Pedro; Larque Daza, Elvira; Lopez Soler, Concepción; Martinez Gracia, Carmen; Martinez Torres, Antonela; Salvador Garcia, Carmen; Sanchez Solis De Querol, Manuel; Yagüe, Genoveva; Zornoza Moreno, Matilde; Santaella-Pascual, Marina; Diego Puente, Teresa de; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Noguera Velasco, José Antonio; Sola Martínez, Rosa Alba; Mendiola Olivares, Jaime; Morales Bartolomé, Eva; Pérez Fernández, Virginia; Torres Cantero, Alberto Manuel; García-Marcos Álvarez, Luis Vicente; Nieto Díaz, Anibal; Prieto Sánchez, María Teresa; Bioquímica y Biología Molecular B e Inmunología
Open Access
Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort
(2020-11-17) García-Serna, Azahara M; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Ballesteros-Meseguer, Carmen; Pérez de los Cobos, Irene; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. Methods: In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. Results: Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 μg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 μg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 μg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. Conclusions: Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.
Open Access
The Nutrition in Early Life and Asthma (NELA) birth cohort study: Rationale, design, and methods.
(Wiley, 2021-09-19) Cabezas Herrera, Juan; Jiménez Guerrero, Pedro; Larque Daza, Elvira; Martinez Gracia, María del Carmen; Martinez Torres, Antonela; Salvador García, Carme; Sánchez Solís De Querol, Manuel; Yagüe Guirao, Genoveva; Zornoza Moreno, Matilde; López Soler, Concepción; Santaella-Pascual, Marina; Diego Puente, Teresa de; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Sola Martínez, Rosa Alba; Noguera Velasco, José Antonio; Mendiola Olivares, Jaime; Morales Bartolomé, Eva; Pérez Fernández, Virginia; Torres Cantero, Alberto Manuel; García-Marcos Álvarez, Luis Vicente; Nieto Díaz, Anibal; Prieto Sánchez, María Teresa; Bioquímica y Biología Molecular B e Inmunología
Background: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. Objectives: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. Population: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19–22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the “Virgen de la Arrixaca” University Clinical Hospital over a 36-month period, from March 2015 to April 2018. Design: Prospective, population-based, maternal-child, birth cohort study. Methods: Questionnaires on exposures and outcome variables were administered to mothers at 20–24 gestation week; 32–36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. Preliminary results: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months’ visit and 532 children (72%) attending the 18 months’ visit. Conclusion: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.
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Serum vitamins A and E at mid-pregnancy and their relationships with both maternal and cord blood antioxidant status and perinatal conditions: The NELA Cohort
(2023-06-02) Sánchez-Campillo, María; Gázquez García, Antonio; Serrano-Munuera, Ana; Bañón Arnao, Marino; Avilés Plaza, Francisco Valeriano; Garcia-Serna, Azahara M.; Noguera Velasco, José Antonio; Martínez López de Castro, Ana María; Martínez Gracia, Carmen; Suárez Martínez, Clara; Santaella-Pascual, Marina; Vioque, Jesús; Montoya-Hernández, Carmen; Ballesteros Meseguer, Carmen; Sánchez Ferrer, María Luisa; Pérez Fernández, Virginia; Morales Bartolomé, Eva; García-Marcos Álvarez, Luis Vicente; Larqué Daza, Elvira; Nela Study Group; Tecnología de Alimentos, Nutrición y Bromatología; Facultad de Veterinaria
Introduction: Most of the pregnant women do not achieve the recommended dietary intake of vitamins A and E. These vitamins may counteract oxidative stress involved in some adverse perinatal outcomes. We aimed to assess the associations between maternal vitamin A and E at mid-pregnancy with both maternal and fetal outcomes and to identify possible early biomarkers during pregnancy to predict and prevent oxidative stress in the offspring. Methods: Data on dietary and serum levels of vitamins A and E were collected from 544 pregnant women from the Nutrition in Early Life and Asthma (NELA) study, a prospective mother-child cohort set up in Spain. Results: There were large discrepancies between low dietary vitamin E intake (78% of the mothers) and low serum vitamin E levels (3%) at 24 weeks of gestation. Maternal serum vitamins A and E at mid-pregnancy were associated with higher antioxidant status not only in the mother at this time point (lower hydroperoxides and higher total antioxidant activity [TAA]) but also with the newborn at birth (higher TAA). Gestational diabetes mellitus (GDM) was negatively associated with maternal serum vitamin A (OR: 0.95 CI: 0.91–0.99, p = 0.009) at mid-pregnancy. Nevertheless, we could not detect any association between GDM and oxidative stress parameters. Conclusions: In conclusion, maternal vitamin A and E serum levels may be used as an early potential biomarker of antioxidant status of the neonate at birth. Control of these vitamins during pregnancy could help avoid morbid conditions in the newborn caused by oxidative stress in GDM pregnancies.
Open Access
Breastmilk polyamines modify gut gene expression in children at three months of age
(Elsevier, 2025-01-22) Sánchez-Campillo, María; Gázquez García, Antonio; Pastor-Fajardo, María T.; López-Andreo, María J.; Pérez-Andrés, Adrián; Martínez Gracia, Carmen; Vioque, Jesús; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Larqué Daza, Elvira; Nela Study Group; Tecnología de Alimentos, Nutrición y Bromatología; Facultad de Veterinaria
Background & aims: Breastmilk is one of the main sources of exogenous polyamines for newborns and contains higher polyamine content than infant formulas. Polyamines are involved in gut maturation and immune system regulation in animals, although the underlying mechanisms are not fully understood. We quantified polyamines in human mature breastmilk and evaluate their effects on intestinal gene expression in babies at three months of age. Methods: Polyamines were quantified in mature milk of 195 women from the prospective Mediterranean NELA birth cohort (Murcia, Spain) at 3 months postpartum. Maternal dietary intake was assessed by food frequency questionnaires. Intestinal gene expression was analysed in babies receiving breastmilk, with high (>p50, n = 25) or low (