Person: Sánchez-Solís de Querol, Manuel
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Inherited epigenetic hallmarks of childhood obesity derived from prenatal exposure to obesogens
Childhood obesity has reached epidemic levels in developed countries and is becoming a major cause for concern in the developing world. The causes of childhood obesity are complex and multifactorial, involving the interaction between individual genetics and environmental and developmental factors. Among the environmental factors, there is a growing interest in understanding the possible relationship between the so-called environmental obesogens and the development of obesity in children. Exposure to these obesogens such as phthalates, bisphenol A, or parabens, has been identified as a promoter of obesity through different mechanisms such as the alteration of adipocyte development from mesenchymal progenitors, the interference with hormone receptors, and induced inflammation. However, less attention has been paid to the inheritance of epigenetic modifications due to maternal exposure to these compounds during pregnancy. Thus, the aim of this review is to summarize the current knowledge of epigenetic modifications due to maternal exposure to those obesogens during pregnancy as well as their potential implication on long-term obesity development in the offspring and transgenerational inheritance of epiphenotypes.
Impact of environmental exposures on exhaled breath and lung function: NELA Birth Cohort
Introduction: Exposure to environmental factors (i.e. air pollution and second-hand tobacco smoke) have been associated with impaired lung function. However, the impact of environmental factors on lung health is usually evaluated separately and not with an exposomic framework. In this regard, breath analysis could be a noninvasive tool for biomonitoring of global human environmental exposure. Methods: Data come from 337 mother-child pairs from the Nutrition in Early Childhood Asthma (NELA) birth cohort. Levels of BTEX (benzene, toluene, ethylbenzene and xylenes) in exhaled breath from mothers and children at 3 months after birth were estimated using gas hromatography-mass spectrometry. Short-term residential exposures (breath sampling day and 15 days before breath sampling) to nitrogen dioxide, particulate matter (PM2.5) and ozone were determined by chemical dispersion/transport modelling. Forced vital capacity, forced expiratory volume in 0.5 s (FEV0.5) and forced expiratory flow at 75% of FVC and at 25%-75% of FVC were measured in infants according to the raised-volume rapid thoracoabdominal compression technique. Results: The results showed significant associations between short-term exposure to external agents and levels of benzene and toluene in exhaled breath. It was observed that exhaled levels of benzene and toluene were influenced by smoking status and outdoor air pollution in mothers, and by air pollution in infants (3 months of age). No significant relationship was observed between exposure to maternal tobacco smoking and/or short-term air pollution and lung function in healthy infants. However, there was a significant relationship between FEV0.5 and exhaled toluene in children. Discussion: These findings indicated a significant relationship between environmental exposures and exhaled levels of benzene and toluene, suggesting that breath analysis could be a helpful exposure biomonitoring tool.
Role of body mass index in unbalanced (dysanaptic) lung growth of healthy infants
Rationale: Imbalance between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) (dysanapsis) has been reported in children who are obese. This dysanaptic growth might begin at an early age, although there are no data on children younger than 6 years. Objetives: To assess whether body mass index (BMI) and early weight gain, in healthy infants born at term, plays a significant role in the imbalance between FEV1 and FVC, even in the absence of obesity. Methods: Lung function was measured by means of raised volume rapid thoracic compression in 69 healthy infants born at term from the Nutrition in Early Life and Asthma cohort. Dysanapsis was defined as zFVC >0.674, zFEV0 .5 ≥-1.645, and FEV0 .5/FVC ≤-1.645. Weight gain (g/day) and growth rate (cm/year) were calculated as the difference between weight and length on the test date and those at birth. To assess the relationship between zBMI and dysanapsis, a receiver operating characteristic curve was performed. Multivariable analysis was carried out by means of linear regressions (one for each lung function index) and by logistic regression for dysanapsis (yes/no). Results: Higher zBMI was associated with risk of dysanapsis (odds ratio: 3.53, [95% confidence interval: 1.30; 9.66]; p = .014): Each additional zBMI unit was associated with ~10 mL higher FVC and with ~3.5% lower FEV0.5/FVC. Weight gain was associated with lower FEV0.5/FVC ratio. Conclusion: Dysanaptic development of lung function begins very early in infancy and is related with weight gain and body mass index, even in the absence of obesity.
Dynamics of the epigenome, microbiome, and metabolome in relation to early adiposity in the maternal–infant axis: protocol for a prospective, observational pilot study in the spanish NEMO cohort
Background: Childhood obesity has reached epidemic levels in developed countries and is an emerging concern in developing regions. Children with excess weight are more likely to maintain this condition over time into adulthood and face a higher risk of developing metabolic disorders such as type 2 diabetes, hypertension, metabolic dysfunction-associated liver disease, and dyslipidemia. Early identification of obesity risk is, therefore, a key public health challenge. Methods: This is an observational, prospective, single-center cohort pilot study in 66 mother–infant dyads recruited at the Gynecology and Obstetrics Service of the Virgen de la Arrixaca University Hospital (Murcia, Spain). The primary objective is to identify early-life, non-invasive biomarkers associated with increased adiposity by integrating multi-omics approaches and analyzing maternal–infant interactions. Pregnant women will be enrolled during the third trimester and will undergo a baseline visit at 38 weeks of gestation for clinical and anthropometric assessment. Buccal swabs and fecal samples will be collected at baseline and in the peripartum period for epigenetic (DNA methylation), metagenomic, and metabolomic analyses. Infants will be evaluated at birth and followed at 6 months, 1 year, 2 years, and 3 years. Each visit will include detailed anthropometric measurements, along with collection of buccal swabs and fecal samples for multi-omics profiling. Conclusions: This multidisciplinary study aims to assess how maternal factors influence infant epigenetic and microbial patterns, and their relation to adiposity development. Early identification of such biomarkers may guide personalized prevention strategies and reduce the long-term burden of obesity-related comorbidities.
Risk factors and bronchopulmonary dysplasia severity: data from the Spanish Bronchopulmonary Dysplasia Research Network
GEIDIS is a national-based research-net registry of patients with bronchopulmonary dysplasia (BPD) from public and private Spanish hospitals. It was created to provide data on the clinical characterization and follow-up of infants with BPD until adulthood. The purpose of this observational study was to analyze the characteristics and the impact of perinatal risk factors on BPD severity. The study included 1755 preterm patients diagnosed with BPD. Of the total sample, 90.6% (n = 1591) were less than 30 weeks of gestation. The median gestational age was 27.1 weeks (25.8-28.5) and median birth weight 885 g (740-1,070 g). A total of 52.5% (n = 922) were classified as mild (type 1), 25.3% (n = 444) were moderate (type 2), and 22.2% (n = 389) were severe BPD (type 3). In patients born at under 30 weeks' gestation, most pre-and postnatal risk factors for type 2/3 BPD were associated with the length of exposure to mechanical ventilation (MV). Independent prenatal risk factors were male gender, oligohydramnios, and intrauterine growth restriction. Postnatal risk factors included the need for FiO2 of > 0.30 in the delivery room, nosocomial pneumonia, and the length of exposure to MV. Conclusion: In this national-based research-net registry of BPD patients, the length of MV is the most important risk factor associated with type 2/3 BPD. Among type 3 BPD patients, those who required an FiO2 > .30 at 36 weeks' postmenstrual age had a higher morbidity, during hospitalization and at discharge, compared to those with nasal positive pressure but FiO2 < .30. What is Known: • BPD is a highly complex multifactorial disease associated with preterm birth. What is New: • The length of exposure to mechanical ventilation is the most important postnatal risk factor associated to bronchopulmonary severity which modulate the effect of most pre and postnatal risk factors. • Among patients with BPD, the requirement for FiO2 >.30% at 36 weeks of postmenstrual age is associated with greater morbidity during hospitalization and at discharge.
Preschool asthma symptoms in children born preterm: the relevance of lung function in infancy
Background: The aim of the study is to assess whether lung function of infants born preterm predicts wheezing in pre-school age. Methods: A survey of the core wheezing questionnaire of the International Study on Asthma and Allergy in Children was administered to parents of preterm newborns, to whom lung function tests were performed at a corrected age of six months, and who, at the time of the survey, were between three and nine years of age. Results: Low values of all lung function parameters measured, except FVC, were predictors of wheezing at some time in life, (FEV0.5 OR: 0.62 (95%CI 0.39; 0.995); FEV0.5/FVC OR: 0.73 (0.54; 0.99)) FEF75 OR: 0.60 [0.37; 0.93]; FEF25-75 OR: 0.57 (0.37; 0.89)); and of wheezing in the past year (FEV0.5 OR: 0.36 (0.17; 0.76); FEV0.5/FVC OR: 0.59 (0.38; 0.93); FEF75 OR: 0.38 [0.19; 0.76]; FEF25-75 OR: 0.35 (0.17; 0.70). In addition, FEV0.5/FVC values lower than the lowest limit of normality, were predictive of hospital admissions due to wheezing (OR: 3.07; (1.02; 9.25)). Conclusions: Limited lung function in infancy is predictive of both future wheezing and hospitalization for a wheezing episode.
La contaminación no es invisible: taller de innovación docente con estudiantes de Medicina
Memoria de innovación docente del taller “La contaminación no es invisible”, desarrollado con estudiantes de 4.º curso de Medicina de la Universidad de Murcia en noviembre de 2023. La actividad integró aprendizaje basado en problemas, sensores ambientales de bajo coste y trabajo práctico sobre contaminación atmosférica interior y exterior, calidad del aire, partículas, óxidos de nitrógeno, compuestos orgánicos volátiles, CO₂ y nitratos en alimentos. El taller incluyó casos clínicos, mediciones en tiempo real, consulta de redes de vigilancia ambiental, reflexión sobre contaminación del Mar Menor y elaboración de propuestas de adaptación y mitigación dirigidas a entornos sanitarios. La memoria recoge la organización de los grupos, actividades realizadas, materiales empleados, comunicación abierta y resultados de evaluación pretest/postest, mostrando mejora significativa en la retención de contenidos entre los participantes. Esta experiencia constituye el origen metodológico de la línea de talleres prácticos #NoEsInvisible, posteriormente reproducida y adaptada en congresos, actividades formativas y foros científicos, como modelo de innovación docente y transferencia de salud medioambiental pediátrica mediante sensores ambientales, casos clínicos y aprendizaje activo.
Child head circumference and placental MFSD2a expression are associated to the level of MFSD2a in maternal blood during pregnancy
Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephalyand intellectual impairments. Herein, we intended to identify early blood biomarkers that maybeofuse during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDMgroups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.
Is low docosahexaenoic acid associated with disturbed rhythms and neurodevelopment in offsprings of diabetic mothers?
BACKGROUND/OBJECTIVE: To evaluate the relation between docosahexaenoic acid (DHA) status and neurodevelopment in the offsprings of gestational diabetic mothers (ODMs). SUBJECTS/METHODS: A prospective cohort study was performed. The offspring of 63 pregnant women (23 controls, 21 diet-controlled gestational diabetes mellitus (GDM) and 19 insulin-treated GDM) were recruited. Maternal and venous cord plasma DHA percentages were analyzed. Skin temperature and activity in children were recorded for 72 h at 3 and 6 months of life. Neurodevelopment was assessed using the Bayley Scale of Infant Development II (BSID II) at 6 and 12 months of age. RESULTS: Cord plasma DHA percentage was significantly lower in the ODMs compared with that in the controls (Control 6.43 [5.04–7.82]a; GDM+diet 5.65 [4.44–6.86]ab; GDM+insulin 5.53 [4.45–6.61]b). Both mental (Control 102.71 [97.61–107.81]a; GDM+diet100.39 [91.43–109.35]a; GDM+insulin 93.94 [88.31–99.57]b) and psychomotor (Control 91.52 [81.82–101.22]a; GDM+diet 81.67[73.95–89.39]b; GDM+insulin 81.89 [71.96–91.85]b) scores evaluated by the BSID II were significantly lower at 6 months in ODMs, even after adjusting for confounding factors such as breastfeeding, maternal educational level and gender. Cord plasma DHA percentage correlated with the psychomotor score from BSID II (r = 0.27; P = 0.049) and with the intra-daily variability in activity (r = − 0.24; P = 0.043) at 6 months. Maternal DHA was correlated with several sleep rhythm maturation parameters at 6 months. CONCLUSIONS: Lower DHA levels in cord plasma of ODMs could affect their neurodevelopment. Maternal DHA status was also associated with higher values in the sleep rhythm maturation parameters of children.
Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: Incidence and results of the national CF-COVID19-Spain survey
Background: Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge is detailed. Methods: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID- 19 Registry is created, requesting information on number of people affected between 8 March–16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed. Results: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accu mulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described. Conclusions: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey.