Sociodemographic, lifestyle, and environmental determinants of vitamin D levels in pregnant women in Spain.

INTRODUCTION: Vitamin D deficiency (<20 ng/mL circulating levels) is a worldwide public health concern and pregnant women are especially vulnerable, affecting the health of the mother and the fetus. This study aims to evaluate the sociodemographic, lifestyle, and environmental determinants associated with circulating vitamin D levels in Spanish pregnant women. METHODS: We used data from the Spanish INMA ("Infancia y Medio Ambiente") prospective birth cohort study from the regions of Gipuzkoa, Sabadell, and Valencia. 25-hydroxyvitamin D3 (25(OH)D3) was measured in plasma collected in the first trimester of pregnancy. Information on 108 determinants was gathered: 13 sociodemographic, 48 lifestyle including diet, smoking and physical activity, and 47 environmental variables, representing the urban and the chemical exposome. Association of the determinants with maternal 25(OH)D3 levels was estimated in single- and multiple-exposure models. Machine learning techniques were used to predict 25(OH)D3 levels below sufficiency (30 ng/mL). RESULTS: The prevalence of < 30 ng/mL 25(OH)D3 levels was 51 %. In the single-exposure analysis, older age, higher socioeconomic status, taking vitamin D, B12 and other sup*plementation, and higher humidity, atmospheric pressure and UV rays were associated with higher levels of 25(OH)D3 (IQR increase of age: 1.2 [95 % CI: 0.6, 1.8] ng/mL 25(OH)D3). In the multiple-exposures model, most of these associations remained and others were revealed. Higher body mass index, PM2.5 and high deprivation area were associated with lower 25(OH)D3 levels (i.e., Quartile 4 of PM2.5 vs Q1: -3.6 [95 % CI: -5.6, -1.5] ng/mL of 25(OH)D3). History of allergy and asthma, being multiparous, intake of vegetable fat, vitamin B6, alcohol consumption and molybdenum were associated with higher levels. The machine learning classification model confirmed some of these associations. CONCLUSIONS: This comprehensive study shows that younger age, higher body mass index, higher deprived areas, higher air pollution and lower UV rays and humidity are associated with lower 25(OH)D3 levels.

Human Milk Feeding Is Associated with Decreased Incidence of Moderate-Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants.

BACKGROUND: An increased rate of bronchopulmonary dysplasia (BPD) is reported in extremely preterm infants. A potential role of human milk feeding in protecting against this condition has been suggested. METHODS: A retrospective descriptive study was conducted based on data about morbidity in the population of infants born between 22+0 and 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and discharged alive. The primary outcome was moderate-severe BPD. Associated conditions were studied, including human milk feeding at discharge. The temporal trends of BPD and human milk feeding rates at discharge were also studied. RESULTS: In the study population of 4341 infants, the rate of moderate-severe BPD was 43.7% and it increased to >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were birth weight, male sex, high-frequency oscillatory ventilation, duration of invasive mechanical ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901 and OR 0.714, 95% CI 0.602-0.847, respectively). During the study period, the proportion of infants with moderate-severe BPD fed any amount of human milk at discharge increased more than twofold. And the proportion of infants with moderate-severe BPD who were exclusively fed human milk at discharge increased at the same rate. CONCLUSIONS: Our work shows an inverse relationship between human milk feeding at discharge from the neonatal unit and the occurrence of BPD.

Improving prediction of COVID-19 mortality using machine learning in the Spanish SEMI-COVID-19 registry.

COVID-19 is responsible for high mortality, but robust machine learning-based predictors of mortality are lacking. To generate a model for predicting mortality in patients hospitalized with COVID-19 using Gradient Boosting Decision Trees (GBDT). The Spanish SEMI-COVID-19 registry includes 24,514 pseudo-anonymized cases of patients hospitalized with COVID-19 from 1 February 2020 to 5 December 2021. This registry was used as a GBDT machine learning model, employing the CatBoost and BorutaShap classifier to select the most relevant indicators and generate a mortality prediction model by risk level, ranging from 0 to 1. The model was validated by separating patients according to admission date, using the period 1 February to 31 December 2020 (first and second waves, pre-vaccination period) for training, and 1 January to 30 November 2021 (vaccination period) for the test group. An ensemble of ten models with different random seeds was constructed, separating 80% of the patients for training and 20% from the end of the training period for cross-validation. The area under the receiver operating characteristics curve (AUC) was used as a performance metric. Clinical and laboratory data from 23,983 patients were analyzed. CatBoost mortality prediction models achieved an AUC performance of 84.76 (standard deviation 0.45) for patients in the test group (potentially vaccinated patients not included in model training) using 16 features. The performance of the 16-parameter GBDT model for predicting COVID-19 hospital mortality, although requiring a relatively large number of predictors, shows a high predictive capacity.

Impact of COVID19 pandemic on patients with rare diseases in Spain, with a special focus on inherited metabolic diseases.

Introduction: The Covid-19 pandemic soon became an international health emergency raising concern about its impact not only on physical health but also on quality of life and mental health. Rare diseases are chronically debilitating conditions with challenging patient care needs. We aimed to assess the quality of life and mental health of patients with rare diseases in Spain, with a special focus on inherited metabolic disorders (IMD). Methods: A prospective case-control study was designed, comparing 459 patients suffering from a rare disease (including 53 patients with IMD) and 446 healthy controls. Quality of life (QoL) and mental health were assessed using validated scales according to age: KINDL-R and the Pediatric Symptom Checklist (PSC) for children and the WhoQoL-Bref questionnaire, GAD and PHQ-9 in adults. Results: First, children and adults (but not adolescents) with IMD showed greater psychological effects than controls (p = 0.022, p = 0.026 respectively). Second, when comparing QoL, only adult patients with IMD showed worse score than controls (66/100 vs 74,6/100 respectively, p = 0.017). Finally, IMD had better quality of life than other rare neurological and genetic diseases (p = 0.008) or other rare diseases (p < 0.001 respectively) but similar alteration of the mental status. Conclusions: Our data show that the pandemic had a negative impact on mental health that is more evident in the group of patients with IMD. Young age would behave as a protective factor on the perception of QoL. Furthermore, patients with IMD show a better QoL than other rare diseases.

Validation of the RIM Score-COVID in the Spanish SEMI-COVID-19 Registry.

The significant impact of COVID-19 worldwide has made it necessary to develop tools to identify patients at high risk of severe disease and death. This work aims to validate the RIM Score-COVID in the SEMI-COVID-19 Registry. The RIM Score-COVID is a simple nomogram with high predictive capacity for in-hospital death due to COVID-19 designed using clinical and analytical parameters of patients diagnosed in the first wave of the pandemic. The nomogram uses five variables measured on arrival to the emergency department (ED): age, sex, oxygen saturation, C-reactive protein level, and neutrophil-to-platelet ratio. Validation was performed in the Spanish SEMI-COVID-19 Registry, which included consecutive patients hospitalized with confirmed COVID-19 in Spain. The cohort was divided into three time periods: T1 from February 1 to June 10, 2020 (first wave), T2 from June 11 to December 31, 2020 (second wave, pre-vaccination period), and T3 from January 1 to December 5, 2021 (vaccination period). The model's accuracy in predicting in-hospital COVID-19 mortality was assessed using the area under the receiver operating characteristics curve (AUROC). Clinical and laboratory data from 22,566 patients were analyzed: 15,976 (70.7%) from T1, 4,233 (18.7%) from T2, and 2,357 from T3 (10.4%). AUROC of the RIM Score-COVID in the entire SEMI-COVID-19 Registry was 0.823 (95%CI 0.819-0.827) and was 0.834 (95%CI 0.830-0.839) in T1, 0.792 (95%CI 0.781-0.803) in T2, and 0.799 (95%CI 0.785-0.813) in T3. The RIM Score-COVID is a simple, easy-to-use method for predicting in-hospital COVID-19 mortality that uses parameters measured in most EDs. This tool showed good predictive ability in successive disease waves.

Active approach in delivery room and survival of infants born between 22 and 26 gestational weeks are increasing in Spain.

AIM: To describe the trends in the delivery room approach and survival of extremely premature infants over the past two decades. METHODS: Time-series analysis of infants included in the Spanish SEN1500 network from 2004 to 2019. Patients born from 22 + 0 to 26 + 6 weeks were included. The primary outcome was an active approach in the delivery room. Survival and temporal trends were also studied. RESULTS: The study population included 8284 patients. At 22 and 23 weeks, an active approach was followed in 41.4% and 80.8%. A temporal trend toward a more active approach was observed at 23 weeks. Antenatal steroids were administered in 19.6% and 58.1% at 22 and 23 weeks. From 24 weeks, an active approach was applied in nearly all cases throughout the period, and more than 80% of patients received antenatal steroids. The rates of survival after an active approach were 8.7%, 21.6%, 40.6%, 59.9%, and 74.7% at 22, 23, 24, 25, and 26 weeks and significantly increased over the period, except for infants born at 22 weeks. CONCLUSION: Active management and survival of infants born from 23 weeks increased over the period, but the frequency of antenatal steroid administration was lower than the intention to resuscitate.

Changes in perinatal management and outcomes in infants born at 23 weeks of gestational age during the last decade in Spain.

INTRODUCTION: The 2021-updated guidelines of the Spanish Society of Neonatology Guidelines have moved the zone of parental discretion to 23 + 0-23 + 6 weeks. The objective of this study was to describe the changes in perinatal management at this gestational age along the last decade and to determine if a more active perinatal management has contributed to improved outcomes. METHODS: Retrospective analysis of prospectively collected data from the 23-week infants included in the Spanish SEN 1500 neonatal network during the period 2010-2019. The main study outcomes were survival at discharge and survival without major morbidity of actively managed infants. Two periods were compared: 2010-2014 (Period 1) and 2015-2019 (Period 2). NICUs were classified into low activity NICUs (less than 50 admissions of very low birth weight infants per year) and high activity NICUs (50 or more admissions). RESULTS: A total of 381 infants were included, 182 in Period 1 and 199 in Period 2. In Period 2 an increase in the use of intrapartum magnesium sulfate (21.5% vs 39.9%, p .002), antenatal steroids (56.6% vs 69.3%, p .011) and active neonatal approach in delivery room (76.9% vs 86.9%, p .011) were observed.The clinical outcomes of the actively managed 313 infants were similar in both periods, except for less arterial hypotension in Period 2. Survival was 27.1% in Period 1 and 25% in Period 2 (p .068) and survival without major morbidity was 2.1% and 2.3% respectively (p .914). No difference was found between low and high activity NICUs. CONCLUSION: A change to a more active intention to treat infants born at 23 weeks is taking place in Spain. But the survival rate of the actively-managed infants has remained stable around 25-30% during the study period. A multidisciplinary effort is needed to improve outcomes in this population.

Children's Health Habits and COVID-19 Lockdown in Catalonia: Implications for Obesity and Non-Communicable Diseases.

Lockdown during the COVID-19 pandemic imposed changes in children's daily routine that could lead to changes in behavior patterns. Using a survey targeted at children under 17 years of age, we described dietary (adherence to Mediterranean diet, AMD) and sleeping habits (disorders of initiating and maintaining sleep) after the implementation of lockdown, and examined the probability of the inadequate frequency of physical activity (PA) and use of TV and electronic devices (TV-ED) before and after lockdown through generalized estimating equation models, accounting for age and gender differences. From 3464 children included, 53.2% showed optimal AMD; 79.2% referred to delayed bedtime; and 16.3% were suspected of sleeping disorders after the implementation of lockdown. Delay in bedtime was more frequent among children older than 6 years, and inadequate sleeping hours among those younger than 11 years. There were no gender differences in AMD or sleeping habits. The odds of inadequate frequency of PA and TV-ED use were greater after lockdown, with a greater risk for TV-ED use. Boys were at greater risk of inadequate PA frequency and TV-ED use. Odds ratio of inadequate PA was greater at older ages. Lockdown could influence changes in children's habits that could lead to risk factors for non-communicable diseases during adulthood if such behaviors are sustained over time.

Hemogram as marker of in-hospital mortality in COVID-19.

The clinical impact of COVID-19 disease calls for the identification of routine variables to identify patients at increased risk of death. Current understanding of moderate-to-severe COVID-19 pathophysiology points toward an underlying cytokine release driving a hyperinflammatory and procoagulant state. In this scenario, white blood cells and platelets play a direct role as effectors of such inflammation and thrombotic response. We investigate whether hemogram-derived ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and the systemic immune-inflammation index may help to identify patients at risk of fatal outcomes. Activated platelets and neutrophils may be playing a decisive role during the thromboinflammatory phase of COVID-19 so, in addition, we introduce and validate a novel marker, the neutrophil-to-platelet ratio (NPR).Two thousand and eighty-eight hospitalized patients with COVID-19 admitted at any of the hospitals of HM Hospitales group in Spain, from March 1 to June 10, 2020, were categorized according to the primary outcome of in-hospital death.Baseline values, as well as the rate of increase of the four ratios analyzed were significantly higher at hospital admission in patients who died than in those who were discharged (p<0.0001). In multivariable logistic regression models, NLR (OR 1.05; 95% CI 1.02 to 1.08, p=0.00035) and NPR (OR 1.23; 95% CI 1.12 to 1.36, p<0.0001) were significantly and independently associated with in-hospital mortality.According to our results, hemogram-derived ratios obtained at hospital admission, as well as the rate of change during hospitalization, may easily detect, primarily using NLR and the novel NPR, patients with COVID-19 at high risk of in-hospital mortality.

Risk Score for Predicting In-Hospital Mortality in COVID-19 (RIM Score).

Infection by SARS-CoV2 has devastating consequences on health care systems. It is a global health priority to identify patients at risk of fatal outcomes. 1955 patients admitted to HM-Hospitales from 1 March to 10 June 2020 due to COVID-19, were were divided into two groups, 1310 belonged to the training cohort and 645 to validation cohort. Four different models were generated to predict in-hospital mortality. Following variables were included: age, sex, oxygen saturation, level of C-reactive-protein, neutrophil-to-platelet-ratio (NPR), neutrophil-to-lymphocyte-ratio (NLR) and the rate of changes of both hemogram ratios (VNLR and VNPR) during the first week after admission. The accuracy of the models in predicting in-hospital mortality were evaluated using the area under the receiver-operator-characteristic curve (AUC). AUC for models including NLR and NPR performed similarly in both cohorts: NLR 0.873 (95% CI: 0.849-0.898), NPR 0.875 (95% CI: 0.851-0.899) in training cohort and NLR 0.856 (95% CI: 0.818-0.895), NPR 0.863 (95% CI: 0.826-0.901) in validation cohort. AUC was 0.885 (95% CI: 0.885-0.919) for VNLR and 0.891 (95% CI: 0.861-0.922) for VNPR in the validation cohort. According to our results, models are useful in predicting in-hospital mortality risk due to COVID-19. The RIM Score proposed is a simple, widely available tool that can help identify patients at risk of fatal outcomes.

[Characteristics of patients with invasive pneumococcal disease requiring admission to intensive care units]. / Características de los pacientes con enfermedad neumocócica invasora que requieren ingreso en la unidad de cuidados intensivos.

INTRODUCTION: Patients with invasive pneumococcal disease (IPD) may require admission into paediatric intensive care units (PICU). The aim of this study is to analyse the epidemiological, clinical, and microbiological characteristics associated with IPD that may require admission to the PICU. MATERIAL AND METHODS: A prospective study was conducted on cases of IPD diagnosed in three Paediatric Hospitals in Barcelona between January 2012 and June 2016. An analysis was made of the associations between the admission to PICU and the epidemiological, clinical, and microbiological variables. RESULTS: A total of 263 cases with IPD were included, of which 19% (n = 50) required admission to PICU. Patients with septic shock (7; 100%), meningitis (16; 84.2%), and those with complicated pneumonia (23; 15.2%) were admitted to the PICU. The most frequent complications were pulmonary (35.2%) and neurological (39.5%). The ratio between admission and non-admission to PICU was 4.7 times higher in subjects with an underlying disease. The serotypes associated with PICU admission were 19A (23% of the total of this serotype), serotype 14 (20%), serotype 3 (17%), and serotype 1 (12.5%). CONCLUSIONS: IPD required PICU admission in cases of septic shock and meningitis, and less so with complicated pneumonia. The percentage of admissions is greater in children with an underlying disease. Admission into the PICU involves a longer stay, complications during the acute phase, as well as sequelae, particularly neurological ones. The serotypes of the patients that were admitted to PICU were predominantly vaccine serotypes.

Ophthalmic Pathology in the Offspring of Pregnant Women with Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes (GD) occurs in 5.8% to 25.1% of pregnant women. This disorder has been linked with intrauterine growth delays, congenital anomalies, and neurobehavioral disorders following birth. As to ophthalmological effects, changes in macular thickness and hypoplasia of the upper quadrant of the papilla have been described. OBJECTIVE: To investigate whether GD has an effect on ophthalmological development in the children born of mothers with this condition. METHODS: Observational study carried out in children seen in the ophthalmological outpatient clinic of a pediatric hospital in Barcelona (Spain) between January 2011 and December 2015. Participants were ultimately divided into two groups, a study group whose mothers had GD managed either by insulin or diet (GD group) and a control group of children with non-diabetic mothers. Pregestational diabetes cases, were excluded. Complete information was collected on the children's refraction status, ophthalmological disease, and congenital malformations. RESULTS: Data were compiled on 350 children (229 children born of mothers with GD-186 managed with diet vs 43, with insulin- and 121 controls). The prevalence of amblyopia and strabismus was similar between the groups, but children of mothers with GD had a three-fold greater probability of having refractive errors than children born to mothers without GD. Hyperopia (14.8% vs. 7.4%) and myopia (3.5% vs 0%) were found to be significantly more prevalent in children born of mothers with GD than in the controls (p = 0.027 in both groups).The prevalence of astigmatism was similar in both groups (1.7% vs 0.8%). CONCLUSIONS FOR PRACTICE: Refractive errors are more common in children born of mothers with GD. These conditions are easily managed, but if they are not detected, they can lead to amblyopia or accommodative strabismus, interfere with acquisition of fine motor skills, and lead to learning problems. Regular ocular examinations would be recommended in these patients.