Maternal antenatal mental health and its associations with perinatal outcomes and the use of healthcare services in children from the NINFEA birth cohort study.

To investigate the associations between maternal mental health disorders before and during pregnancy and perinatal outcomes and child healthcare utilization between 6 and 18 months of age. Among the 6814 mother-child pairs from the Italian Internet-based NINFEA birth cohort, maternal depression, anxiety, and sleep disorders diagnosed by a physician before and during pregnancy were assessed through self-reported questionnaires completed during pregnancy and 6 months after delivery. Perinatal outcomes (preterm birth, birth weight, small for gestational age, congenital anomalies, and neonatal intensive care unit (NICU)) and children's healthcare utilization (emergency department (ED) visits, hospitalizations, and outpatient visits) were reported by mothers at 6 and 18 months postpartum. We used regression models adjusted for maternal age, education, parity, country of birth, region of delivery, and household income. Maternal mental health disorders were not associated with perinatal outcomes, except for depression, which increased the risk of offspring admission to NICU, and anxiety disorders during pregnancy, which were associated with preterm birth and lower birth weight. Children born to mothers with depression/anxiety disorders before pregnancy, compared to children of mothers without these disorders, had an increased odds of a visit to ED for any reason (odds ratio (ORadj) = 1.26, 95% confidence interval (CI): 1.02-1.54), of an ED visit resulting in hospitalization (ORadj = 1.75, 95%CI: 1.27-2.42), and of planned hospital admissions (ORadj = 1.55, 95%CI: 1.01-2.40). These associations with healthcare utilization were similar for mental disorders also during pregnancy. The association pattern of maternal sleep disorders with perinatal outcomes and child healthcare utilization resembled that of maternal depression and/or anxiety disorders with these outcomes.   Conclusion: Antenatal maternal mental health is a potential risk factor for child-health outcomes and healthcare use. Early maternal mental health interventions may help to promote child health and reduce healthcare costs. What is Known: • Poor maternal mental health affects pregnancy outcomes and child health, and children of mothers with mental health conditions tend to have increased healtcare utilization. • Parents with poor mental health often face challenges in caring for their children and have less parenting self-efficacy, which could potentially lead to frequent medical consultations for minor health issues. What is New: • Maternal pre-pregnancy mental disorders were not associated with preterm birth, low birth weight, SGA, and congenital anomalies, except for depression, which increased the risk of offspring admission to NICU. Anxiety disorders during pregnancy were associated with lower birth weight and an increased odds of preterm birth. • Maternal depression and/or anxiety and sleep disorders, both before and during pregnancy, were associated with an increase in children's healthcare utilization between 6 and 18 months of life.

Socioeconomic position, family context, and child cognitive development.

Socioeconomic position (SEP) may have different effects on cognitive development and family context could play a role in this association. This work aimed to analyse the role of socioeconomic positions, measured via various indicators collected longitudinally, in cognitive development at 7-11 years of age, evaluating the role of family context as a potential mediator. The study sample included 394 and 382 children from the INMA Gipuzkoa and Valencia cohorts, respectively. SEP indicators were assessed during pregnancy (family social class, parental education, employment, and disposable income) and at 7 (Gipuzkoa) and 11 (Valencia) years of age (At Risk of Poverty or Social Exclusion (AROPE)). Family context and cognitive development were measured with the Haezi-Etxadi Family Assessment Scale 7-11 (HEFAS 7-11) and Raven's Coloured Progressive Matrices (Raven's CPM), respectively. Linear regression models were developed to assess the relationships between (a) SEP-family context, (b) SEP-cognitive development, and (c) family context-cognitive development, adjusting for a priori-selected confounders. Simple and multiple mediation analyses were performed to explore the role of family context in the SEP-cognitive development relationship. Lower SEP was related with a lower cognitive score, this association being particularly robust for family social class. SEP indicators were related to subscales of family context, in particular those regarding cognitive stimulation, parental stress, and parenting. A relationship was also found between these three subscales and child cognitive development, mediating the effect of family social class on child cognition by 5.2, 5.5, and 10.8%, respectively, and 12.0% jointly.    Conclusion: Both family SEP and context contribute to a child's cognitive development. Equalising policies and positive parenting programmes could contribute to improving cognitive development in children. What is Known: • Parental social class, education, and employment status have been widely employed to measure socioeconomic position. What is New: • This work focuses on standard measurements of socioeconomic position but also other economic indicators such as the EHII and AROPE, and their effect on child cognitive development and family context. • Promotion of cognitive and linguistic development, parental stress and conflict, and parental profile fostering child development mediated the effect of family social class on cognitive development.

Examining the relationship between the environmental impact of diet and child growth from a co-benefit perspective.

The adoption of diets that minimize both their environmental impacts and weight excess in children would be a major co-benefit for climate change mitigation. We evaluated the relationship between child diet-related environmental impact and anthropometric characteristics in an Italian birth cohort. The study involved 2127 children of the Piccolipiù birth cohort. At 4 years, their diet in the previous two months was assessed through a questionnaire, from which we derived individual: (i) diet-related daily greenhouse gas emissions (GHGE), (ii) land use (LU), (iii) adherence to the Mediterranean Diet (MD) and (iv) red meat consumption. We related these variables with overweight and obesity, waist circumference, and height at 4 years using regression models adjusted for a priori selected confounders. Diet-related GHGE and LU had a positive weak association with overweight and obesity, with an odds ratio (OR) for the fourth vs. second quartile of 1.30 for both GHGE (95% confidence intervals -CI-: 0.96; 1.77) and LU (95% CI: 0.96-1.76). Both OR estimates increased after adjustment for energy intake. GHGE and LU were not associated with height, with the exception of shorter children in the first quartile. A high vs. low MD adherence was associated with an increase in height Z-score of 0.11 (95% CI 0.01; 0.21). No association was found for red meat consumption. These results suggest that lowering the impact of high environmental impact diets may have, if anything, beneficial effects on child obesity, overweight, and height, with pro-MD patterns playing an important role.

Family socioeconomic position and changes in planned health care for children with chronic diseases during the COVID-19 pandemic in Italy.

Introduction: In this study, we aimed at evaluating whether, during the COVID-19 pandemic, children affected by chronic diseases were impacted by the deferral of planned healthcare caused by the restriction measures. Design: This study was conducted using data from the Italian NINFEA birth cohort, which include children born between 2005 and 2016. Women who completed the 4-year NINFEA follow-up questionnaire before November 2020 (N = 5,307) were invited to complete a questionnaire targeted at evaluating the impacts of the pandemic on their children's health. The questionnaire asked mothers to report whether their children had a chronic disease or condition that required one or more regular health checks by a doctor in 2019 (used as a reference period) and whether the children had problems getting routine health checks after March 2020. Results: We obtained information on 3,721 children. Out of 353 children with a chronic disease that required at least one medical visit in 2019, 130 (36.8%) experienced problems during the pandemic. Lower family income was associated with a higher risk of experiencing health access problems. We observed that children living in families at lower income tertiles had more chance of experiencing healthcare access problems than children living in families at the highest income tertiles (prevalence rate ratio for a tertile decrease in family income: 1.22; 95% CIs: 1.02-1.49). Conclusion: Our study underlines that the COVID-19 pandemic may have caused healthcare access problems for children with prevalent chronic diseases, especially among those living in households with a low socioeconomic position.

[Exposome: from definition to future challenges.] / Esposoma: dalla definizione alle sfide future.

The exposome concept arises from the need to integrate different disciplines of public health and environmental sciences, mainly including environmental epidemiology, exposure science, and toxicology. The role of the exposome is to understand how the totality of an individual's exposures throughout the lifetime can impact human health. The etiology of a health condition is rarely explained by a single exposure. Therefore, examining the human exposome as a whole becomes relevant to simultaneously consider multiple risk factors and more accurately estimate concurrent causes of different health outcomes. Generally, the exposome is explained through three domains: general external exposome, specific external exposome, and internal exposome. The general external exposome includes measurable population-level exposures such as air pollution or meteorological factors. The specific external exposome includes information on individual exposures, such as lifestyle factors, typically obtained from questionnaires. Meanwhile, the internal exposome encompasses multiple biological responses to external factors, detected through molecular and omics analyses. Additionally, in recent decades, the socio-exposome theory has emerged, where all exposures are studied as a phenomenon dependent on the interaction between socioeconomic factors that vary depending on the context, allowing the identification of mechanisms that lead to health inequalities. The considerable production of data in exposome studies has led researchers to face new methodological and statistical challenges, introducing various approaches to estimate the effect of the exposome on health. Among the most common are regression models (Exposome-Wide Association Study - ExWAS), dimensionality reduction and exposure grouping techniques, and machine learning methods. The significant conceptual and methodological innovation of the exposome for a more holistic evaluation of the risks associated with human health is continuously expanding and will require further investigations related to the application of information obtained from studies into prevention and public health policies.

Correction: Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

[This corrects the article DOI: 10.1371/journal.pmed.1004036.].

The impact of income-support interventions on life course risk factors and health outcomes during childhood: a systematic review in high income countries.

BACKGROUND: In high income countries one in five children still lives in poverty, which is known to adversely shape the life course health trajectory of these children. However, much less is understood on whether social and fiscal policies have the capacity to reverse this damage, which intervention is likely to be most effective and when these interventions should be delivered to maximise their impact. This systematic review attempts to address these questions by looking at the impact of income-support interventions, delivered during the first 1,000 days of life, on cardiovascular, metabolic, respiratory and mental health outcomes. METHODS: The review was restricted to experimental or quasi experimental studies conducted in high income countries. Studies were retrieved from multidisciplinary databases as well as health, economic, social sciences-specific literature browsers. All papers retrieved through the search strategy were double screened at title, abstract and full text stage. Relevant data of the selected studies were extracted and collected in tables, then summarised via narrative synthesis approach. Robustness of findings was assessed by tabulating impact by health outcome, type of intervention and study design. RESULTS: Overall, 16 relevant papers were identified, including 15 quasi-experimental studies and one randomized control trial (RCT). Income-support interventions included were unconditional/conditional cash transfers, income tax credit and minimum wage salary policies. Most studies were conducted in United States and Canada. Overall, the evidence suggested limited effect on mental health indicators but a positive, albeit small, effect of most policies on birth weight outcomes. Despite this, according to few studies that tried to extrapolate the results into public health terms, the potential number of negative outcomes averted might be consistent. CONCLUSIONS: Income-support interventions can positively affect some of the health outcomes of interest in this review, including birth weight and mental health. Given the large number of people targeted by these programs, one could infer that - despite small - the observed effect may be still relevant at population level. Nonetheless, the limited generalisability of the evidence gathered hampers firm conclusions. For the future, the breadth and scope of this literature need to be broadened to fully exploit the potential of these interventions and understand how their public health impact can be maximised.

Modelling socioeconomic position as a driver of the exposome in the first 18 months of life of the NINFEA birth cohort children.

BACKGROUND: The exposome drivers are less studied than its consequences but may be crucial in identifying population subgroups with unfavourable exposures. OBJECTIVES: We used three approaches to study the socioeconomic position (SEP) as a driver of the early-life exposome in Turin children of the NINFEA cohort (Italy). METHODS: Forty-two environmental exposures, collected at 18 months of age (N = 1989), were classified in 5 groups (lifestyle, diet, meteoclimatic, traffic-related, built environment). We performed cluster analysis to identify subjects sharing similar exposures, and intra-exposome-group Principal Component Analysis (PCA) to reduce the dimensionality. SEP at childbirth was measured through the Equivalised Household Income Indicator. SEP-exposome association was evaluated using: 1) an Exposome Wide Association Study (ExWAS), a one-exposure (SEP) one-outcome (exposome) approach; 2) multinomial regression of cluster membership on SEP; 3) regressions of each intra-exposome-group PC on SEP. RESULTS: In the ExWAS, medium/low SEP children were more exposed to greenness, pet ownership, passive smoking, TV screen and sugar; less exposed to NO2, NOX, PM25abs, humidity, built environment, traffic load, unhealthy food facilities, fruit, vegetables, eggs, grain products, and childcare than high SEP children. Medium/low SEP children were more likely to belong to a cluster with poor diet, less air pollution, and to live in the suburbs than high SEP children. Medium/low SEP children were more exposed to lifestyle PC1 (unhealthy lifestyle) and diet PC2 (unhealthy diet), and less exposed to PC1s of the built environment (urbanization factors), diet (mixed diet), and traffic (air pollution) than high SEP children. CONCLUSIONS: The three approaches provided consistent and complementary results, suggesting that children with lower SEP are less exposed to urbanization factors and more exposed to unhealthy lifestyles and diet. The simplest method, the ExWAS, conveys most of the information and is more replicable in other populations. Clustering and PCA may facilitate results interpretation and communication.

Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. METHODS AND FINDINGS: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. CONCLUSIONS: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

A multicenter prospective study validated a nomogram to predict individual risk of dependence in ambulation after rehabilitation.

OBJECTIVES: To develop the Functional Risk Index for Dependence in Ambulation (FRIDA) score, a nomogram to predict individual risk of dependence in ambulation at discharge from postacute rehabilitation and validate its performance temporally and spatially. STUDY DESIGN AND SETTING: We analyzed the database of a multicenter prospective observational quality cohort study conducted from January 2012 to March 2016, including data from 8,796 consecutive inpatients who underwent rehabilitation after stroke, hip fracture, lower limb joint replacement, debility, and other neurologic, orthopedic, or miscellaneous conditions. RESULTS: A total of 3,026 patients (34.4%) were discharged dependent in ambulation. In the training set of 5,162 patients (58.7%), Lasso-regression selected advanced age, premorbid disability, and eight indicators of medical and functional adverse syndromes at baseline to establish the FRIDA score. At the temporal validation obtained on an external set of 3,234 patients (41.3%), meta-analyses showed that the FRIDA score had good and homogeneous discrimination (summary area under the curve 0.841, 95% confidence interval = 0.826-0.855, I2 = 0.00%) combined with accurate calibration (summary Log O/E ratio 0.017, 95% confidence interval -0.155 to 0.190). These performances remained stable at spatial validation obtained on 3,626 patients, with substantial heterogeneity of estimates across nine facilities. Decision curve analyses showed that a FRIDA score-supported strategy far outperformed the usual "treat all" approach in each impairment categories. CONCLUSION: The FRIDA score is a new clinically useful tool to predict an individual risk for dependence in ambulation at rehabilitation discharge in many different disabilities, and may also reflect well the case-mix composition of the rehabilitation facilities.

Exposure to natural environments during pregnancy and birth outcomes in 11 European birth cohorts.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Unintentional injuries and potential determinants of falls in young children: Results from the Piccolipiù Italian birth cohort.

OBJECTIVES: Unintentional injuries such as falls, are particularly frequent in early childhood. To date, epidemiological studies in this field have been carried out using routine data sources or registries and many studies were observational studies with a cross-sectional design. The aims of the study are to describe unintentional injuries in the first two years of life in the Piccolipiù birth cohort, and to investigate the association between mother and children characteristics and the First Event of Raised surface Fall (FERF). METHODS: This longitudinal observational study included 3038 children from an Italian birth cohort. Data on socio-demographic factors, socio-economic indicators, maternal health and lifestyle characteristics and child's sleeping behavior, obtained from questionnaires completed at birth, 12 and 24 months of age, were considered in the analyses as potential risk factors of FERF. Time of occurrence of FERF was analyzed using the Kaplan-Meier method. The multivariable analysis for time to event was carried out using a Cox proportional hazards model. RESULTS: Falls from raised surfaces are the leading cause of unintentional injuries in the cohort with 610 (21.1%) and 577 (20.0%) cases among children during the first and second year of life, respectively. An increased risk of FERF was associated with several risk factors: maternal psychological distress (HR 1.41, 95%CI 1.10-1.81), maternal alcohol intake (HR 1.26, 95%CI 1.10-1.45), and child's sleeping problems (HR 1.28, 95%CI 1.09-1.51). Children with older aged mothers (HR 0.98, 95%CI 0.96-0.99) and living in northern Italy (HR 0.64, 95%CI 0.55-0.75) had a lower risk of FERF. CONCLUSION: The results of the study suggest that a higher risk of FERF is associated with socio-demographic factors, maternal characteristics and child sleeping behavior that could hinder parent empowerment.

Extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS. METHODS: This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients' characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications. RESULTS: Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17-2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78-2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients. CONCLUSION: In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference. TRIAL REGISTRATION NUMBER: NCT05080933 , retrospectively registered.

Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network.

BACKGROUND: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. OBJECTIVE: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. METHODS: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. RESULTS: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. CONCLUSION: Our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.

Prenatal exposure to PM10 and changes in DNA methylation and telomere length in cord blood.

BACKGROUND: Air pollution exposure in pregnancy can cause molecular level alterations that might influence later disease susceptibility. OBJECTIVES: We investigated DNA methylation (DNAm) and telomere length (TL) in the cord blood in relation to gestational PM10 exposure and explored potential gestational windows of susceptibility. METHODS: Cord blood epigenome-wide DNAm (N = 384) and TL (N = 500) were measured in children of the Italian birth cohort Piccolipiù, using the Infinium Methylation EPIC BeadChip and qPCR, respectively. PM10 daily exposure levels, based on maternal residential address, were estimated for different gestational periods using models based on satellite data. Epigenome-wide analysis to identify differentially methylated probes (DMPs) and regions (DMRs) was conducted, followed by a pathway analysis and replication analysis in an second Piccolipiù dataset. Distributed lag models (DLMs) using weekly exposures were used to study the association of PM10 exposure across pregnancy with telomere length, as well as with the DMPs that showed robust associations. RESULTS: Gestational PM10 exposure was associated with the DNA methylation of more than 250 unique DMPs, most of them identified in early gestation, and 1 DMR. Out of 151 DMPs available in the replication dataset, ten DMPs showed robust associations: eight were associated with exposure during early gestation and 2 with exposure during the whole pregnancy. These exposure windows were supported by the DLM analysis. The PM10 exposure between 15th and 20th gestational week seem to be associated with shorter telomeres at birth, while exposure between 24th and 29th was associated with longer telomeres. DISCUSSION: The early pregnancy period is a potential critical window during which PM10 exposure can influence cord blood DNA methylation. The results from the TL analysis were consistent with previous findings and merit further exploration in future studies. The study underlines the importance of considering gestational windows outside of the predefined trimesters that may not always overlap with biologically relevant windows of exposure.

Developing an integrated microsimulation model for the impact of fiscal policies on child health in Europe: the example of childhood obesity in Italy.

BACKGROUND: We developed an integrated model called Microsimulation for Income and Child Health (MICH) that provides a tool for analysing the prospective effects of fiscal policies on childhood health in European countries. The aim of this first MICH study is to evaluate the impact of alternative fiscal policies on childhood overweight and obesity in Italy. METHODS: MICH model is composed of three integrated modules. Firstly, module 1 (M1) simulates the effects of fiscal policies on disposable household income using the tax-benefit microsimulation program EUROMOD fed with the Italian EU-SILC 2010 data. Secondly, module 2 (M2) exploits data provided by the Italian birth cohort called Nascita e Infanzia: gli Effetti dell'Ambiente (NINFEA), translated as Birth and Childhood: the Effects of the Environment study, and runs a series of concatenated regressions in order to estimate the prospective effects of income on child body mass index (BMI) at different ages. Finally, module 3 (M3) uses dynamic microsimulation techniques that combine the population structure and incomes obtained by M1, with regression model specifications and estimated effect sizes provided by M2, projecting BMI distributions according to the simulated policy scenarios. RESULTS: Both universal benefits, such as universal basic income (BI), and targeted interventions, such as child benefit (CB) for poorer households, have a significant effect on childhood overweight, with a prevalence ratio (PR) in 10-year-old children-in comparison with the baseline fiscal system-of 0.88 (95%CI 0.82-0.93) and 0.89 (95%CI 0.83-0.94), respectively. The impact of the fiscal reforms was even larger for child obesity, reaching a PR of 0.67 (95%CI 0·50-0.83) for the simulated BI and 0.64 (95%CI 0.44-0.84) for CB at the same age. While both types of policies show similar effects, the estimated costs for a 1% prevalence reduction in overweight and obesity with respect to the baseline scenario is much lower with a more focalised benefit policy than with universal ones. CONCLUSIONS: Our results show that fiscal policies can have a strong impact on childhood health conditions. Focalised interventions that increase family income, especially in the most vulnerable populations, can help to prevent child overweight and obesity. Robust microsimulation models to forecast the effects of fiscal policies on health should be considered as one of the instruments to reach the Health in All Policies (HiAP) goals.

COVID-19-like symptoms and their relation to the SARS-CoV-2 epidemic in children and adults of an Italian birth cohort

OBJECTIVES: to estimate the population prevalence of COVID-19-like symptoms in children and adults during the first SARS-CoV-2 epidemic wave hitting Italy in the spring 2020; to assess their geographical correlation with the cumulative number of COVID-19 cases by province; to analyse their clustering within families; to estimate their sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for COVID-19 diagnosis in individuals tested for SARS-CoV-2. DESIGN: cross-sectional study nested within a birth cohort. SETTING AND PARTICIPANTS: mothers participating in an Italian birth cohort (NINFEA) were invited to complete an online questionnaire on COVID-19-like symptoms in their household. MAIN OUTCOME MEASURES: population prevalence of COVID-19-like symptoms in children and adults, geographical correlation of COVID-19-like symptoms with the cumulative number of COVID-19 cases by province, clustering of COVID-19-like symptoms within families, and sensitivity, PPV and NPV of COVID-19-like symptoms for COVID-19 diagnosis in individuals tested for SARS-CoV-2. RESULTS: information was collected on 3,184 households, 6,133 adults, and 5,751 children. In the period March-April 2020, 55.4% of the NINFEA families had at least one member with at least one COVID-19-like symptom. There was a strong geographical correlation between the population cumulative incidence of COVID-19 and the prevalence of muscle pain, fatigue, low-grade fever, and breathing difficulties in adults (Spearman's rho >=0.70). Having at least one family member with a COVID-19 diagnosis, compared with none tested for SARS-CoV-2, was associated with an increased prevalence ratio (PR) of almost all COVID-19-like symptoms in adults, and only of low-grade fever (37-37.5°C; PR 4.54; 95%CI 2.20-9.40) and anosmia/dysgeusia in children. Among adults with COVID-19 diagnosis, fatigue, muscle pain, and fever had a sensitivity >=70%. In individuals tested for SARS-CoV-2, with a 16.6% prevalence of COVID-19, breathing difficulties and nausea/vomiting had the highest PPVs, with point estimates close to 60%, and with NPVs close to 90%. CONCLUSIONS: the geographical prevalence of COVID-19-like symptoms in adults may inform on local disease clusters, while certain symptoms in family members of confirmed COVID-19 cases could help identify the intra-familial spread of the virus and its further propagation in the community. Low-grade fever is frequent in children with at least one household member with COVID-19 and possibly indicates child infection.

Effects of Steroids and Tocilizumab on the Immune Response Profile of Patients with COVID-19-Associated ARDS Requiring or Not Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving rescue therapy in patients with Acute Respiratory Distress Syndrome (ARDS). ECMO has been associated with development of lymphocytopenia that is also common in COVID-19. Hyperinflammation may complicate SARS-CoV-2 pneumonia, prompting therapy with steroids and immunomodulatory drugs. We aimed to evaluate the association of therapies such as steroids and Tocilizumab with trajectories of the total leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers in COVID-19-related ARDS, requiring or not VV-ECMO support. The association of the trajectories of the leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers with treatment with steroids (Steroids), Tocilizumab (Tocilizumab), both drugs (Steroids + Tocilizumab), and absence of treatment (No Treatment) were analyzed using mixed effects regression models, where ECMO was considered as a potential effect modifier. One hundred and thirty-nine leukocyte and eighty-one lymphocyte subpopulation counts were obtained from thirty-one patients who required (VV-ECMO, N = 13) or not (no VV-ECMO, N = 18) extracorporeal support. In both groups, treatment with Steroids + Tocilizumab was independently associated with a significant reduction of 46% and 67% in total lymphocytes, 22% and 60% in CD3+, and 61% and 91% in CD19+ (B lymphocytes) compared to those obtained without treatment, respectively. In the no VV-ECMO group, Tocilizumab was associated with a 79% increase in total lymphocytes and with a reduction in procalcitonin compared to no treatment. CD45+, CD3+CD4+ (Th cell), CD3+CD8+, CD4+/CD8+, the NK cell subpopulation, neutrophils, monocytes, and basophils were significantly reduced by Steroids + Tocilizumab without an effect modification by VV-ECMO support. In critically ill COVID-19 patients with ARDS, concomitant therapies with steroids and Tocilizumab, beside mitigating the inflammation and fibrinolysis, could reduce the total leukocyte, lymphocyte, and subpopulation count. Moreover, the effect of Tocilizumab in increasing the total lymphocytes and reducing procalcitonin might be blunted by VV-ECMO.

Medication burden and clustering in people living with HIV undergoing therapeutic drug monitoring.

AIM: People living with HIV (PLWH) have a high burden of comorbidities and concomitant medication use. The aim of this study was to analyse the prevalence, predictors and patterns of polypharmacy (PP) in a large therapeutic drug monitoring (TDM) registry. METHODS: We searched our TDM registry and categorized co-medications into 26 drug classes. We included patients with at least one medication recorded: PP and severe polypharmacy (sPP) were defined as the concomitant use of ≥5 or ≥10 nonantiretroviral/nonantitubercular drugs. Multivariable binary logistic analysis were conducted for identifying PP/sPP predictors. A hierarchical average-linkage cluster analysis was performed among drug classes. RESULTS: We included 2432 participants (1158 PLWH) aged 49.6 years (± 14.4) in the 2016-2020 period. A higher number of concomitant medications (4 vs 3.1, P < .001) and a higher prevalence of PP (26.1% vs 21.8%, P = .015) were recorded in controls. At multivariable binary logistic analysis older age, female gender and HIV-positive serostatus (P = .015) were independent predictors of PP; older age and year of inclusion were independent predictors of sPP. Cluster analysis showed that patients receiving oral drug for type 2 diabetes have a high probability of receiving several other drugs; a cluster of co-medications was observed with opioids, diuretics and central nervous system-affecting drugs. CONCLUSION: We observed a moderately high prevalence of polypharmacy in middle-aged PLWH: advanced age and female gender were associated with the greatest prevalence. The observation of co-medication clusters suggests groups of comorbidities but also identifies groups of patients at risk of similar drug-to-drug interactions.

Determination of saliva epigenetic age in infancy, and its association with parental socio-economic characteristics and pregnancy outcomes.

Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7-17) months were used to estimate Horvath's DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: -0.79 to 2.34 for low/medium education; 0.96, 95% CI: -1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath's method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.